Vol. 29 (2024)
| No. 01 | DOI: 10.1186/s11658-023-00527-9 Volume 29 (2024) - 29:01 | |
| Title | CORRECTION: ClC-2 KNOCKDOWN PREVENTS CEREBROVASCULAR REMODELING VIA INHIBITION OF THE Wnt/β-CATENIN SIGNALING PATHWAY | |
| Authors | Jingjing Lu1, Feng Xu2, Yingna Zhang3, Hong Lu4 & Jiewen Zhang1* | |
| Abstract | Correction: Cellular & Molecular Biology Letters (2018) 23:29 https://doi.org/10.1186/s11658-018-0095-z Following publication of the original article [1], the authors informed us that there is in Fig. 3C. The pictures used in the AngII and AngII + Negative groups in Fig. 3C were repeated. Neither of these changes affects the results and conclusions of this study. The original article can be found online at https://doi.org/10.1186/s11658-018-0095-z. | |
| Keywords | ||
| Address and Contact Information |
1 Department of Neurology, Henan People’s Hospital, No. 7 Wai-5 Road, Zhengzhou 450052, Henan, China 2 Department of Urology, First Affiliated Hospital, Zhengzhou University, Zhengzhou, China 3 Institute of Medical and Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, China 4 Department of Neurology, First Affiliated Hospital, Zhengzhou University, Zhengzhou 450052, Henan, China *Corresponding author: HZ_Sammy@163.com |
|
| Read full article at BMC | ||
| No. 02 | DOI: 10.1186/s11658-023-00523-z Volume 29 (2024) - 29:02 | |
| Title | TRANSFER RNA-DERIVED SMALL RNA tRF-Glu-CTC ATTENUATES NEOINTIMAL FORMATION VIA INHIBITION OF FIBROMODULIN | |
| Authors | Qi‐Lan Jiang1, Jia‐Ying Xu2, Qing‐Ping Yao3, Rui Jiang4, Qin Xu2, Bo‐Tao Zhang2, Tao Li5* and Jun Jiang2* | |
| Abstract | Neointimal hyperplasia is a pathological vascular remodeling caused by abnormal proliferation and migration of subintimal vascular smooth muscle cells (VSMCs) following intimal injury. There is increasing evidence that tRNA-derived small RNA (tsRNA) plays an important role in vascular remodeling. The purpose of this study is to search for tsRNAs signature of neointima formation and to explore their potential functions. The balloon injury model of rat common carotid artery was replicated to induce intimal hyperplasia, and the differentially expressed tsRNAs (DE-tsRNAs) in arteries with intimal hyperplasia were screened by small RNA sequencing and tsRNA library. A total of 24 DE-tsRNAs were found in the vessels with intimal hyperplasia by small RNA sequencing. In vitro, tRF-Glu-CTC inhibited the expression of fibromodulin (FMOD) in VSMCs, which is a negative modulator of TGF-β1 activity. tRF-Glu-CTC also increased VSMC proliferation and migration. In vivo experiments showed that inhibition of tRF-Glu-CTC expression after balloon injury of rat carotid artery can reduce the neointimal area. In conclusion, tRF-Glu-CTC expression is increased after vascular injury and inhibits FMOD expression in VSMCs, which influences neointima formation. On the other hand, reducing the expression of tRF-Glu-CTC after vascular injury may be a potential approach to prevent vascular stenosis. | |
| Keywords | Transfer RNA (tRNA)-derived small RNAs (tsRNAs), Vascular smooth muscle cell, Vascular remodeling, Neointimal hyperplasia (NIH), Proliferation, Migration | |
| Address and Contact Information |
1 Department of Clinical Nutrition, Afliated Hospital of Southwest Medical University, Luzhou, Sichuan Province, China 2 Department of General Surgery (Thyroid Surgery), The Afliated Hospital of Southwest Medical University, 25 Taiping Street, Jiangyang District, Luzhou 646000, Sichuan Province, China 3 Institute of Mechanobiology and Medical Engineering, School of Life Science and Biotechnology, Shanghai Jiao Tong University, Shanghai, China 4 Department of Urology, Afliated Hospital of Southwest Medical University, Luzhou, Sichuan Province, China 5 Key Laboratory of Medical Electrophysiology of Ministry of Education, Collaborative Innovation Center for Prevention and Treatment of Cardiovascular Disease, Institute of Cardiovascular Research, Southwest Medical University, Luzhou 646000, Sichuan Province, China *Corresponding author: leta49@swmu.edu.cn; jiangjun@swmu.edu.cn |
|
| Read full article at BMC | ||
| No. 03 | DOI: 10.1186/s11658-023-00520-2 Volume 29 (2024) - 29:03 | |
| Title | CIRCULAR RNA-circPan3 ATTENUATES CARDIAC HYPERTROPHY VIA miR-320-3p/HSP20 AXIS | |
| Authors | Xinyu Fang1, Xiang Ao1, Dandan Xiao1, Yu Wang1, Yi Jia1, Peiyan Wang1, Mengyang Li1* and Jianxun Wang1* | |
| Abstract | Background:
Circular RNAs are enriched in cardiac tissue and play important roles in the pathogenesis of heart diseases. In this study, we aimed to investigate the regulatory mechanism of a conserved heart-enriched circRNA, circPan3, in cardiac hypertrophy. Methods: Cardiac hypertrophy was induced by isoproterenol. The progression of cardiomyocyte hypertrophy was assessed by sarcomere organization staining, cell surface area measurement, and expression levels of cardiac hypertrophy markers. RNA interactions were detected by RNA pull-down assays, and methylated RNA immunoprecipitation was used to detect m6A level. Results: The expression of circPan3 was downregulated in an isoproterenol-induced cardiac hypertrophy model. Forced expression of circPan3 attenuated cardiomyocyte hypertrophy, while inhibition of circPan3 aggravated cardiomyocyte hypertrophy. Mechanistically, circPan3 was an endogenous sponge of miR-320-3p without affecting miR-320-3p levels. It elevated the expression of HSP20 by endogenously interacting with miR-320-3p. In addition, circPan3 was N6-methylated. Stimulation by isoproterenol downregulated the m6A eraser ALKBH5, resulting in N6-methylation and destabilization of circPan3. Conclusions: Our research is the first to report that circPan3 has an antihypertrophic effect in cardiomyocytes and revealed a novel circPan3-modulated signalling pathway involved in cardiac hypertrophy. CircPan3 inhibits cardiac hypertrophy by targeting the miR-320-3p/HSP20 axis and is regulated by ALKBH5-mediated N6-methylation. This pathway could provide potential therapeutic targets for cardiac hypertrophy. | |
| Keywords | Cardiac hypertrophy, m6A modifcation, Circular RNA, circPan3, miR- 320-3p, HSP20 | |
| Address and Contact Information |
1 School of Basic Medicine, Qingdao University, Qingdao 266071, China *Corresponding author: limengyang@qdu.edu.cn; wangjx@qdu.edu.cn |
|
| Read full article at BMC | ||
| No. 04 | DOI: 10.1186/s11658-023-00521-1 Volume 29 (2024) - 29:04 | |
| Title | THE REGULATORY RELATIONSHIP BETWEEN TRANSCRIPTION FACTOR STAT3 AND NONCODING RNA | |
| Authors | Siyi Liu1,2, Wentao Li2, Lin Liang2, Yanhong Zhou2* and Yanling Li1* | |
| Abstract | Signal transducer and activator of transcription 3 (STAT3), as a key node in numerous carcinogenic signaling pathways, is activated in various tumor tissues and plays important roles in tumor formation, metastasis, and drug resistance. STAT3 is considered a potential subtarget for tumor therapy. Noncoding RNA (ncRNA) is a special type of RNA transcript. Transforming from “junk” transcripts into key molecules involved in cell apoptosis, growth, and functional regulation, ncRNA has been proven to be closely related to various epithelial–mesenchymal transition and drug resistance processes in tumor cells over the past few decades. Research on the relationship between transcription factor STAT3 and ncRNAs has attracted increased attention. To date, existing reviews have mainly focused on the regulation by ncRNAs on the transcription factor STAT3; there has been no review of the regulation by STAT3 on ncRNAs. However, understanding the regulation of ncRNAs by STAT3 and its mechanism is important to comprehensively understand the mutual regulatory relationship between STAT3 and ncRNAs. Therefore, in this review, we summarize the regulation by transcription factor STAT3 on long noncoding RNA, microRNA, and circular RNA and its possible mechanisms. In addition, we provide an update on research progress on the regulation of STAT3 by ncRNAs. This will provide a new perspective to comprehensively understand the regulatory relationship between transcription factor STAT3 and ncRNAs, as well as targeting STAT3 or ncRNAs to treat diseases such as tumors. | |
| Keywords | circRNA, LncRNA, microRNA, STAT3, Transcription factor | |
| Address and Contact Information |
1 Department of Nuclear Medicine, Hunan Cancer Hospital and The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha 410013, China 2 Cancer Research Institute, Basic School of Medicine, Central South University, Changsha 410011, Hunan, China *Corresponding author: zhouyanhong@csu.edu.cn; liyanling@hnca.org.cn |
|
| Read full article at BMC | ||
| No. 05 | DOI: 10.1186/s11658-023-00522-0 Volume 29 (2024) - 29:05 | |
| Title | MYCT1 INHIBITS HEMATOPOIESIS IN DIFFUSE LARGE B-CELL LYMPHOMA BY SUPPRESSING RUNX1 TRANSCRIPTION | |
| Authors | Ying Liang1,2, Xin Wei2, Peng‐Jie Yue2, He‐Cheng Zhang1, Zhen‐Ning Li3, Xiao‐Xue Wang2, Yuan‐Yuan Sun1* and Wei‐Neng Fu1* | |
| Abstract |
Background:
The abnormality of chromosomal karyotype is one factor causing poor prognosis of lymphoma. In the analysis of abnormal karyotype of lymphoma patients, three smallest overlap regions were found, in which MYCT1 was located. MYCT1 is the first tumor suppressor gene cloned by our research team, but its studies relating to the occurrence and development of lymphoma have not been reported. Methods: R banding analyses were employed to screen the abnormality of chromosomal karyotype in clinical specimen and MYCT1 over-expression cell lines. FISH was to monitor MYCT1 copy number aberration. RT-PCR and Western blot were to detect the mRNA and protein levels of the MYCT1 and RUNX1 genes, respectively. The MYCT1 and RUNX1 protein levels in clinical specimen were evaluated by immunohistochemical DAB staining. The interaction between MYCT1 and MAX proteins was identified via Co-IP and IF. The binding of MAX on the promoter of the RUNX1 gene was detected by ChIP and Dual-luciferase reporter assay, respectively. Flow cytometry and CCK-8 assay were to explore the effects of MYCT1 and RUNX1 on the cell cycle and proliferation, respectively. Results: MYCT1 was located in one of three smallest overlap regions of diffuse large B-cell lymphoma, it altered chromosomal instability of diffuse large B-cell lymphoma cells. MYCT1 negatively correlated with RUNX1 in lymphoma tissues of the patients. MAX directly promoted the RUNX1 gene transcription by binding to its promoter region. MYCT1 may represses RUNX1 transcription by binding MAX in diffuse large B-cell lymphoma cells. MYCT1 binding to MAX probably suppressed RUNX1 transcription, leading to the inhibition of proliferation and cell cycle of the diffuse large B-cell lymphoma cells. Conclusion: This study finds that there is a MYCT1-MAX-RUNX1 signaling pathway in diffuse large B-cell lymphoma. And the study provides clues and basis for the in-depth studies of MYCT1 in the diagnosis, treatment and prognosis of lymphoma. | |
| Keywords | MYCT1, Difuse large B-cell lymphoma, Chromosomal karyotype | |
| Address and Contact Information |
1 Department of Medical Genetics, China Medical University, No. 77 Puhe Road, Shenyang North New Area, Shenyang, Liaoning Province 110122, People’s Republic of China 2 Department of Hematology, The First Affiliated Hospital of China Medical University, Shenyang 110001, People’s Republic of China 3 Department of Oromaxillofacial‐Head and Neck Surgery, Liaoning Province Key Laboratory of Oral Disease, School and Hospital of Stomatology, China Medical University, Shenyang, People’s Republic of China *Corresponding author: yysun@cmu.edu.cn; wnfu@cmu.edu.cn |
|
| Read full article at BMC | ||
| No. 06 | DOI: 10.1186/s11658-023-00519-9 Volume 29 (2024) - 29:06 | |
| Title | ONCOGENIC ACTIVATION OF EEF1A2 EXPRESSION: A JOURNEY FROM A PUTATIVE TO AN ESTABLISHED ONCOGENE | |
| Authors | Saket Awadhesbhai Patel1,2, Md. Khurshidul Hassan1,2 and Manjusha Dixit1,2* | |
| Abstract | Protein synthesis via translation is a central process involving several essential proteins called translation factors. Although traditionally described as cellular “housekeepers,” multiple studies have now supported that protein initiation and elongation factors regulate cell growth, apoptosis, and tumorigenesis. One such translation factor is eukaryotic elongation factor 1 alpha 2 (EEF1A2), a member of the eukaryotic elongation factor family, which has a canonical role in the delivery of aminoacyl-tRNA to the A-site of the ribosome in a guanosine 5′-triphosphate (GTP)-dependent manner. EEF1A2 differs from its closely related isoform, EEF1A1, in tissue distribution. While EEF1A1 is present ubiquitously, EEF1A2 replaces it in specialized tissues. The reason why certain specialized tissues need to essentially switch EEF1A1 expression altogether with EEF1A2 remains to be answered. Abnormal “switch on” of the EEF1A2 gene in normal tissues is witnessed and is seen as a cause of oncogenic transformation in a wide variety of solid tumors. This review presents the journey of finding increased expression of EEF1A2 in multiple cancers, establishing molecular mechanism, and exploring it as a target for cancer therapy. More precisely, we have compiled studies in seven types of cancers that have reported EEF1A2 overexpression. We have discussed the effect of aberrant EEF1A2 expression on the oncogenic properties of cells, signaling pathways, and interacting partners of EEF1A2. More importantly, in the last part, we have discussed the unique potential of EEF1A2 as a therapeutic target. This review article gives an up-to-date account of EEF1A2 as an oncogene and can draw the attention of the scientific community, attracting more research. | |
| Keywords | Cancer, EEF1A1, EEF1A2, PI3K, AKT | |
| Address and Contact Information |
1 School of Biological Sciences, National Institute of Science Education and Research, Room No. 204, P.O. Jatni, Khurda, Bhubaneswar, Odisha 752050, India 2 Homi Bhabha National Institute, Training School Complex, Anushaktinagar, Mumbai 400094, India *Corresponding author: manjusha@niser.ac.in |
|
| Read full article at BMC | ||
| No. 07 | DOI: 10.1186/s11658-023-00516-y Volume 29 (2024) - 29:07 | |
| Title | THE PYROPTOSIS MEDIATED BIOMARKER PATTERN: AN EMERGING DIAGNOSTIC APPROACH FOR PARKINSON’S DISEASE | |
| Authors | Junhan Liang1, Zhirong Wan2, Cheng Qian1, Madiha Rasheed1, Changling Cao1, Jingyan Sun3, Xuezhe Wang1, Zixuan Chen1* and Yulin Deng1* | |
| Abstract | Background:
Parkinson’s disease (PD) affects 1% of people over 60, and long-term levodopa treatment can cause side effects. Early diagnosis is of great significance in slowing down the pathological process of PD. Multiple pieces of evidence showed that non-coding RNAs (ncRNAs) could participate in the progression of PD pathology. Pyroptosis is known to be regulated by ncRNAs as a key pathological feature of PD. Therefore, evaluating ncRNAs and pyroptosis-related proteins in serum could be worthy biomarkers for early diagnosis of PD. Methods: NcRNAs and pyroptosis/inflammation mRNA levels were measured with reverse transcriptase quantitative polymerase chain reaction (RT-qPCR). Luciferase assays were performed to confirm GSDME as a target of miR-675-5p and HMGB1 as a target of miR-1247-5p. In the serum of healthy controls (n = 106) and PD patients (n = 104), RT-qPCR was utilized to assess miR-675-5p, miR-1247-5p, and two related ncRNAs (circSLC8A1and lncH19) levels. The enzyme-linked immunosorbent assay measured serum levels of pyroptosis-related proteins in controls (n = 54) and PD patients (n = 70). Results: Our data demonstrated that miR-675-5p and miR-1247-5p significantly changed in PD neuron and animal models. Overexpressed miR-675-5p or downregulated miR-1247-5p could regulate pyroptosis and inflammation in PD neuron models. Using the random forest algorithm, we constructed a classifier based on PD neuron-pyroptosis pathology (four ncRNAs and six proteins) having better predictive power than single biomarkers (AUC = 92%). Additionally, we verified the performance of the classifier in early-stage PD patients (AUC ≥ 88%). Conclusion: Serum pyroptosis-related ncRNAs and proteins could serve as reliable, inexpensive, and non-invasive diagnostic biomarkers for PD. | |
| Keywords | Parkinson’s disease, Biomarker patterns, Machine learning | |
| Address and Contact Information |
1 Beijing Key Laboratory for Separation and Analysis in Biomedicine and Pharmaceuticals, School of Medical Technology, Beijing Institute of Technology, Zhongguancun South Street, Haidian District, Beijing 100081, People’s Republic of China 2 Department of Neurology, Aerospace Center Hospital, Beijing 100049, People’s Republic of China 3 School of Life Sciences, Beijing Institute of Technology, Beijing 100081, People’s Republic of China *Corresponding author: zx-chen@bit.edu.cn; deng@bit.deu.cn |
|
| Read full article at BMC | ||
| No. 08 | DOI: 10.1186/s11658-023-00529-7 Volume 29 (2024) - 29:08 | |
| Title | IDH1/MDH1 DEACETYLATION PROMOTES ACUTE LIVER FAILURE BY REGULATING NETosis | |
| Authors | Yukun Wang1, Chunxia Shi1, Jin Guo1, Danmei Zhang1, Yanqiong Zhang1, Long Zhang1 and Zuojiong Gong1* | |
| Abstract | Background:
Acute liver failure (ALF) is a life-threatening disease, but its pathogenesis is not fully understood. NETosis is a novel mode of cell death. Although the formation of neutrophil extracellular traps (NETs) has been found in various liver diseases, the specific mechanism by which NETosis regulates the development of ALF is unclear. In this article, we explore the role and mechanism of NETosis in the pathogenesis of ALF. Methods: Clinically, we evaluated NETs-related markers in the liver and peripheral neutrophils of patients with ALF. In in vitro experiments, HL-60 cells were first induced to differentiate into neutrophil-like cells (dHL-60 cells) with dimethyl sulfoxide (DMSO). NETs were formed by inducing dHL-60 cells with PMA. In in vivo experiments, the ALF model in mice was established with LPS/D-gal, and the release of NETs was detected by immunofluorescence staining and western blotting. Finally, the acetylation levels of IDH1 and MDH1 were detected in dHL-60 cells and liver samples by immunoprecipitation. Results: Clinically, increased release of NETs in liver tissue was observed in patients with ALF, and NETs formation was detected in neutrophils from patients with liver failure. In dHL-60 cells, mutations at IDH1-K93 and MDH1-K118 deacetylate IDH1 and MDH1, which promotes the formation of NETs. In a mouse model of ALF, deacetylation of IDH1 and MDH1 resulted in NETosis and promoted the progression of acute liver failure. Conclusions: Deacetylation of IDH1 and MDH1 reduces their activity and promotes the formation of NETs. This change aggravates the progression of acute liver failure. | |
| Keywords | Deacetylation, Acute liver failure, NETosis | |
| Address and Contact Information |
1 Department of Infectious Diseases, Renmin Hospital of Wuhan University, 238 Jiefang Road, Wuhan 430060, China *Corresponding author: zjgong@163.com |
|
| Read full article at BMC | ||
| No. 09 | DOI: 10.1186/s11658-023-00525-x Volume 29 (2024) - 29:09 | |
| Title | MYH1G-AS IS A CHROMATIN-ASSOCIATED lncRNA THAT REGULATES SKELETAL MUSCLE DEVELOPMENT IN CHICKEN | |
| Authors | Bolin Cai1,2, Manting Ma1,2, Rongshuai Yuan1,2, Zhen Zhou1,2, Jing Zhang3, Shaofen Kong1,2, Duo Lin1,2, Ling Lian4, Juan Li5, Xiquan Zhang1,2 and Qinghua Nie1,2* | |
| Abstract | Background Skeletal muscle development is pivotal for animal growth and health. Recently, long noncoding RNAs (lncRNAs) were found to interact with chromatin through diverse roles. However, little is known about how lncRNAs act as chromatin-associated RNAs to regulate skeletal muscle development. Here, we aim to investigate the regulation of chromatin-associated RNA (MYH1G-AS) during skeletal muscle development. Methods We provided comprehensive insight into the RNA profile and chromatin accessibility of different myofibers, combining RNA sequencing (RNA-seq) with an assay for transposase-accessible chromatin with high-throughput sequencing (ATAC-seq). The dual-luciferase reporter assay and chromatin immunoprecipitation (ChIP) assay were used to analyze the transcriptional regulation mechanism of MYH1G-AS. ALKBH5-mediated MYH1G-AS N6-methyladenosine (m6A) demethylation was assessed by a single-base elongation and ligation-based qPCR amplification method (SELECT) assay. Functions of MYH1G-AS were investigated through a primary myoblast and lentivirus/cholesterol-modified antisense oligonucleotide (ASO)-mediated animal model. To validate the interaction of MYH1G-AS with fibroblast growth factor 18 (FGF18) protein, RNA pull down and an RNA immunoprecipitation (RIP) assay were performed. Specifically, the interaction between FGF18 and SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily A member 5 (SMARCA5) protein was analyzed by coimmunoprecipitation (Co-IP) and a yeast two-hybrid assay. Results A total of 45 differentially expressed (DE) lncRNAs, with DE ATAC-seq peaks in their promoter region, were classified as open chromatin-associated lncRNAs. A skeletal muscle-specific lncRNA (MSTRG.15576.9; MYH1G-AS), which is one of the open chromatin-associated lncRNA, was identified. MYH1G-AS transcription is coordinately regulated by transcription factors (TF) SMAD3 and SP2. Moreover, SP2 represses ALKBH5 transcription to weaken ALKBH5-mediated m6A demethylation of MYH1G-AS, thus destroying MYH1G-AS RNA stability. MYH1G-AS accelerates myoblast proliferation but restrains myoblast differentiation. Moreover, MYH1G-AS drives a switch from slow-twitch to fast-twitch fibers and causes muscle atrophy. Mechanistically, MYH1G-AS inhibits FGF18 protein stabilization to reduce the interaction of FGF18 to SMARCA5, thus repressing chromatin accessibility of the SMAD4 promoter to activate the SMAD4-dependent pathway. Conclusions Our results reveal a new pattern of the regulation of lncRNA expression at diverse levels and help expound the regulation of m6A methylation on chromatin status. | |
| Keywords | Chromatin accessibility, LncRNA MYH1G-AS, m6A methylation, Skeletal muscle development | |
| Address and Contact Information |
1 State Key Laboratory of Livestock and Poultry Breeding, Guangdong Laboratory for Lingnan Modern Agriculture, College of Animal Science, South China Agricultural University, Guangzhou, China 2 Guangdong Provincial Key Lab of Agro-Animal Genomics and Molecular Breeding, Key Laboratory of Chicken Genetics, Breeding and Reproduction, Ministry of Agriculture and Rural Affairs, National-Local Joint Engineering Research Center for Livestock Breeding, Guangzhou, China 3 Randall Centre of Cell and Molecular Biophysics, Faculty of Life Sciences and Medicine, New Hunt’s House, King’s College London, Guy’s Campus, London, UK 4 National Engineering Laboratory for Animal Breeding and MOA Key Laboratory of Animal Genetics and Breeding, College of Animal Science and Technology, China Agricultural University, Beijing,China 5 Key Laboratory of Bio-Resources and Eco-Environment of Ministry of Education, College of Life Sciences, Sichuan University, Chengdu, China *Corresponding author: nqinghua@scau.edu.cn |
|
| Read full article at BMC | ||
| No. 10 | DOI: 10.1186/s11658-023-00526-w Volume 29 (2024) - 29:10 | |
| Title | THE EFFICACY OF ADIPOSE-DERIVED STEM CELLS IN BURN INJURIES: A SYSTEMATIC REVIEW | |
| Authors | Michael Kohlhauser1*, Alexandru Tuca1,2 and Lars‐Peter Kamolz1,3 | |
| Abstract | Background:
Burn injuries can be associated with prolonged healing, infection, a substantial inflammatory response, extensive scarring, and eventually death. In recent decades, both the mortality rates and long-term survival of severe burn victims have improved significantly, and burn care research has increasingly focused on a better quality of life post-trauma. However, delayed healing, infection, pain and extensive scar formation remain a major challenge in the treatment of burns. ADSCs, a distinct type of mesenchymal stem cells, have been shown to improve the healing process. The aim of this review is to evaluate the efficacy of ADSCs in the treatment of burn injuries. Methods: A systematic review of the literature was conducted using the electronic databases PubMed, Web of Science and Embase. The basic research question was formulated with the PICO framework, whereby the usage of ADSCs in the treatment of burns in vivo was determined as the fundamental inclusion criterion. Additionally, pertinent journals focusing on burns and their treatment were screened manually for eligible studies. The review was registered in PROSPERO and reported according to the PRISMA statement. Results: Of the 599 publications screened, 21 were considered relevant to the key question and were included in the present review. The included studies were almost all conducted on rodents, with one exception, where pigs were investigated. 13 of the studies examined the treatment of full-thickness and eight of deep partial-thickness burn injuries. 57,1 percent of the relevant studies have demonstrated that ADSCs exhibit immunomodulatory effects during the inflammatory response. 16 studies have shown improved neovascularisation with the use of ADSCs. 14 studies report positive influences of ADSCs on granulation tissue formation, while 11 studies highlight their efficacy in promoting re-epithelialisation. 11 trials demonstrated an improvement in outcomes during the remodelling phase. Conclusion: In conclusion, it appears that adipose-derived stem cells demonstrate remarkable efficacy in the field of regenerative medicine. However, the usage of ADSCs in the treatment of burns is still at an early experimental stage, and further investigations are required in order to examine the potential usage of ADSCs in future clinical burn care. | |
| Keywords | Adipose-derived stem cells, Mesenchymal stem cells, Stem cell research, Burns, Burn injury, Burn care, Tissue engineering, Regenerative medicine, Wound healing | |
| Address and Contact Information |
1 Division of Plastic, Aesthetic and Reconstructive Surgery, Department of Surgery, Medical University of Graz, Graz, Austria 2 Department of Surgery, State Hospital Güssing, Güssing, Austria 3 COREMED‐Cooperative Centre for Regenerative Medicine, JOANNEUM RESEARCH Forschungsgesellschaft mbH, Graz, Austria *Corresponding author: michael.kohlhauser@medunigraz.at |
|
| Read full article at BMC | ||
| No. 11 | DOI: 10.1186/s11658-023-00524-y Volume 29 (2024) - 29:11 | |
| Title | RETRACTION NOTE: INHIBITION OF INFLAMMATION USING DIACEREIN MARKEDLY IMPROVED RENAL FUNCTION IN ENDOTOXEMIC ACUTE KIDNEY INJURED MICE | |
| Authors | Guangzhe Yu1, Qian Liu2, Xuening Dong2, Kaihong Tang2, Bohui Li2, Chunmei Liu2, Wenzheng Zhang2, Yiduo Wang2 and Yingyu Jin2* | |
| Abstract |
The Original Article was published on 16 August 2018 Retraction: Cellular & Molecular Biology Letters (2018) 23:38 https://doi.org/10.1186/s11658-018-0107-z
The authors stated that they used third-party services to obtain some of their data. The Editor-in-Chief, therefore, has lost confidence in the integrity of the article's findings. We contacted the authors on the emails they provided at submission. Yingyu Jin has stated on behalf of the authors that they agree to this retraction. | |
| Keywords | ||
| Address and Contact Information |
1 Department of Emergency Surgery, The 1st Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang Province, China 2 Department of Laboratory Diagnosis, The 1st Affiliated Hospital of Harbin Medical University, 23 Youzheng Street, Nangang District, Harbin 150001, Heilongjiang Province, People’s Republic of China *Corresponding author: yingyu_jin@163.com |
|
| Read full article at BMC | ||
| No. 12 | DOI: 10.1186/s11658-023-00530-0 Volume 29 (2024) - 29:12 | |
| Title | INCREASED SERUM EXTRACHROMOSOMAL CIRCULAR DNA SORBS1circle LEVEL IS ASSOCIATED WITH INSULIN RESISTANCE IN PATIENTS WITH NEWLY DIAGNOSED TYPE 2 DIABETES MELLITUS | |
| Authors | Xiang Kong1,2,3†, Shu‐jun Wan1,3†, Tian‐bing Chen1,3†, Lan Jiang1,3, Yu‐jie Xing1,2, Ya‐ping Bai1, Qiang Hua4, Xin‐ming Yao4, Yong‐li Zhao4, Hong‐mei Zhang5, De‐guo Wang2*, Qing Su5* and Kun Lv1,3* | |
| Abstract | Background:
Extrachromosomal circular DNAs (eccDNAs) exist in human blood and somatic cells, and are essential for oncogene plasticity and drug resistance. However, the presence and impact of eccDNAs in type 2 diabetes mellitus (T2DM) remains inadequately understood. Methods: We purified and sequenced the serum eccDNAs obtained from newly diagnosed T2DM patients and normal control (NC) subjects using Circle-sequencing. We validated the level of a novel circulating eccDNA named sorbin and SH3‐domain‐ containing‐1circle97206791–97208025 (SORBS1circle) in 106 newly diagnosed T2DM patients. The relationship between eccDNA SORBS1circle and clinical data was analyzed. Furthermore, we explored the source and expression level of eccDNA SORBS1circle in the high glucose and palmitate (HG/PA)-induced hepatocyte (HepG2 cell) insulin resistance model. Results: A total of 22,543 and 19,195 eccDNAs were found in serum samples obtained from newly diagnosed T2DM patients and NC subjects, respectively. The T2DM patients had a greater distribution of eccDNA on chromosomes 1, 14, 16, 17, 18, 19, 20 and X. Additionally, 598 serum eccDNAs were found to be upregulated, while 856 eccDNAs were downregulated in T2DM patients compared with NC subjects. KEGG analysis demonstrated that the genes carried by eccDNAs were mainly associated with insulin resistance. Moreover, it was validated that the eccDNA SORBS1circle was significantly increased in serum of newly diagnosed T2DM patients (106 T2DM patients vs. 40 NC subjects). The serum eccDNA SORBS1circle content was positively correlated with the levels of glycosylated hemoglobin A1C (HbA1C) and homeostasis model assessment of insulin resistance (HOMA-IR) in T2DM patients. Intracellular eccDNA SORBS1circle expression was significantly enhanced in the high glucose and palmitate (HG/PA)-induced hepatocyte (HepG2 cell) insulin resistance model. Moreover, the upregulation of eccDNA SORBS1circle in the HG/PA-treated HepG2 cells was dependent on generation of apoptotic DNA fragmentation. Conclusions: These results provide a preliminary understanding of the circulating eccDNA patterns at the early stage of T2DM and suggest that eccDNA SORBS1circle may be involved in the development of insulin resistance. | |
| Keywords | Extrachromosomal circular DNAs, T2DM, SORBS1, Insulin resistance | |
| Address and Contact Information |
1 Anhui Provincial Key Laboratory of Non‐Coding RNA Basic and Clinical Transformation, Wannan Medical College, Wuhu 241002, China 2 Geriatric Endocrinology Unit, Department of Gerontology, The First Affiliated Hospital of Wannan Medical College, Yijishan Hospital, Wuhu 241001, China 3 Central Laboratory of Yijishan Hospital, Wuhu 241001, China 4 Department of Endocrinology, The First Affiliated Hospital of Wannan Medical College, Yijishan Hospital, Wuhu 241001, China 5 Department of Endocrinology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200092, China *Corresponding author: wangdeguo@medmail.com.cn; suqing@xinhuamed.com.cn; lvkun315@126.com † Xiang Kong, Shu-jun Wan and Tian-bing Chen contributed equally to this work. |
|
| Read full article at BMC | ||
| No. 13 | DOI: 10.1186/s11658-023-00528-8 Volume 29 (2024) - 29:13 | |
| Title | MULTIPRONGED REGULATION OF AUTOPHAGY AND APOPTOSIS: EMERGING ROLE OF TRIM PROTEINS | |
| Authors | Nuzhat Ahsan1*†, Mohd Shariq1†, Avadhesha Surolia2*, Reshmi Raj1, Mohammad Firoz Khan1 and Pramod Kumar1 | |
| Abstract | TRIM proteins are characterized by their conserved N-terminal RING, B-box, and coiled-coil domains. These proteins are efficient regulators of autophagy, apoptosis, and innate immune responses and confer immunity against viruses and bacteria. TRIMs function as receptors or scaffold proteins that target substrates for autophagy-mediated degradation. Most TRIMs interact with the BECN1-ULK1 complex to form TRIMosomes, thereby efficiently targeting substrates to autophagosomes. They regulate the functions of ATG proteins through physical interactions or ubiquitination. TRIMs affect the lipidation of MAP1LC3B1 to form MAP1LC3B2, which is a prerequisite for phagophore and autophagosome formation. In addition, they regulate MTOR kinase and TFEB, thereby regulating the expression of ATG genes. TRIM proteins are efficient regulators of apoptosis and are crucial for regulating cell proliferation and tumor formation. Many TRIM proteins regulate intrinsic and extrinsic apoptosis via the cell surface receptors TGFBR2, TNFRSF1A, and FAS. Mitochondria modulate the anti- and proapoptotic functions of BCL2, BAX, BAK1, and CYCS. These proteins use a multipronged approach to regulate the intrinsic and extrinsic apoptotic pathways, culminating in coordinated activation or inhibition of the initiator and executor CASPs. Furthermore, TRIMs can have a dual effect in determining cell fate and are therefore crucial for cellular homeostasis. In this review, we discuss mechanistic insights into the role of TRIM proteins in regulating autophagy and apoptosis, which can be used to better understand cellular physiology. These findings can be used to develop therapeutic interventions to prevent or treat multiple genetic and infectious diseases. | |
| Keywords | TRIM proteins, E3-Ub ligase, Apoptosis, Autophagy, Ubiquitination, Autophagosome, BECN1, ULK1, TP53, Autophagy receptor | |
| Address and Contact Information |
1 Quantlase Lab LLC, Unit 1-8, Masdar City, Abu Dhabi, UAE 2 Molecular Biophysics Unit, Indian Institute of Science, Bangalore 460012, India *Corresponding author: nuzhat.ahsan@quantlase. ae; nuzhatahsan@gmail.com; surolia@iisc.ac.in † Nuzhat Ahsan and Mohd Shariq are contributed equally to this work. |
|
| Read full article at BMC | ||
| No. 14 | DOI: 10.1186/s11658-024-00531-7 Volume 29 (2024) - 29:14 | |
| Title | MECHANISTIC ROLE OF QUERCETIN AS INHIBITOR FOR ADENOSINE DEAMINASE ENZYME IN RHEUMATOID ARTHRITIS: SYSTEMATIC REVIEW | |
| Authors | Amira Atta1, Maha M. Salem1*, Karim Samy El‐Said1 and Tarek M. Mohamed1 | |
| Abstract | Rheumatoid arthritis (RA) is an autoimmune disease involving T and B lymphocytes. Autoantibodies contribute to joint deterioration and worsening symptoms. Adenosine deaminase (ADA), an enzyme in purine metabolism, influences adenosine levels and joint inflammation. Inhibiting ADA could impact RA progression. Intracellular ATP breakdown generates adenosine, which increases in hypoxic and inflammatory conditions. Lymphocytes with ADA play a role in RA. Inhibiting lymphocytic ADA activity has an immune-regulatory effect. Synovial fluid levels of ADA are closely associated with the disease’s systemic activity, making it a useful parameter for evaluating joint inflammation. Flavonoids, such as quercetin (QUE), are natural substances that can inhibit ADA activity. QUE demonstrates immune-regulatory effects and restores T-cell homeostasis, making it a promising candidate for RA therapy. In this review, we will explore the impact of QUE in suppressing ADA and reducing produced the inflammation in RA, including preclinical investigations and clinical trials. | |
| Keywords | Rheumatoid arthritis, Adenosine deaminase, Flavonoid, Quercetin, Synovial fuid | |
| Address and Contact Information |
1 Biochemistry Division, Chemistry Department, Faculty of Science, Tanta University, Tanta 31527, Egypt *Corresponding author: maha_salem@science.tanta.edu.eg |
|
| Read full article at BMC | ||
| No. 15 | DOI: 10.1186/s11658-024-00533-5 Volume 29 (2024) - 29:15 | |
| Title | SUMOylation MODULATES eIF5A ACTIVITIES IN BOTH YEAST AND PANCREATIC DUCTAL ADENOCARCINOMA CELLS | |
| Authors | Rocío Seoane1,7, Tomás Lama‐Díaz1,2, Antonia María Romero3,15, Ahmed El Motiam1,16, Arantxa Martínez‐Férriz4, Santiago Vidal1,7, Yanis H. Bouzaher1, María Blanquer1, Rocío M. Tolosa1, Juan Castillo Mewa5, Manuel S. Rodríguez6, Adolfo García‐Sastre7,8,9,10, Dimitris Xirodimas11, James D. Sutherland12, Rosa Barrio12, Paula Alepuz3,13, Miguel G. Blanco1,2, Rosa Farràs4 and Carmen Rivas1,14* | |
| Abstract | Background:
The eukaryotic translation initiation protein eIF5A is a highly conserved and essential factor that plays a critical role in different physiological and pathological processes including stress response and cancer. Different proteomic studies suggest that eIF5A may be a small ubiquitin-like modifier (SUMO) substrate, but whether eIF5A is indeed SUMOylated and how relevant is this modification for eIF5A activities are still unknown. Methods: SUMOylation was evaluated using in vitro SUMOylation assays, Histidine-tagged proteins purification from His6–SUMO2 transfected cells, and isolation of endogenously SUMOylated proteins using SUMO-binding entities (SUBES). Mutants were engineered by site-directed mutagenesis. Protein stability was measured by a cycloheximide chase assay. Protein localization was determined using immunofluorescence and cellular fractionation assays. The ability of eIF5A1 constructs to complement the growth of Saccharomyces cerevisiae strains harboring thermosensitive mutants of a yeast EIF5A homolog gene (HYP2) was analyzed. The polysome profile and the formation of stress granules in cells expressing Pab1–GFP (a stress granule marker) by immunofluorescence were determined in yeast cells subjected to heat shock. Cell growth and migration of pancreatic ductal adenocarcinoma PANC-1 cells overexpressing different eIF5A1 constructs were evaluated using crystal violet staining and transwell inserts, respectively. Statistical analysis was performed with GraphPad Software, using unpaired Student’s t-test, or one-way or two-way analysis of variance (ANOVA). Results: We found that eIF5A is modified by SUMO2 in vitro, in transfected cells and under endogenous conditions, revealing its physiological relevance. We identified several SUMO sites in eIF5A and found that SUMOylation modulates both the stability and the localization of eIF5A in mammalian cells. Interestingly, the SUMOylation of eIF5A responds to specific stresses, indicating that it is a regulated process. SUMOylation of eIF5A is conserved in yeast, the eIF5A SUMOylation mutants are unable to completely suppress the defects of HYP2 mutants, and SUMOylation of eIF5A is important for both stress granules formation and disassembly of polysomes induced by heat-shock. Moreover, mutation of the SUMOylation sites in eIF5A abolishes its promigratory and proproliferative activities in PANC-1 cells. Conclusions: SUMO2 conjugation to eIF5A is a stress-induced response implicated in the adaptation of yeast cells to heat-shock stress and required to promote the growth and migration of pancreatic ductal adenocarcinoma cells. | |
| Keywords | eIF5A, Pancreatic ductal adenocarcinoma, Stress granules, Stress response, SUMO2 | |
| Address and Contact Information |
1 Centro de Investigación en Medicina Molecular (CIMUS), IDIS, Universidade de Santiago de Compostela, Avda Barcelona, 15706 Santiago de Compostela, Spain. 2 Departamento de Bioquímica e Bioloxía Molecular, Universidade de Santiago de Compostela, 15706 Santiago de Compostela, Spain. 3 Departamento de Bioquímica y Biología Molecular, Facultad de Ciencias Biológicas, Universitat de València, Burjassot, 46100 Valencia, Spain. 4 Centro de Investigación Príncipe Felipe, 46012 Valencia, Spain. 5 Research Department in Genomics and Proteomics, Instituto Conmemorativo Gorgas de Estudios de la Salud, 0816‐02593 Panamá, Republic of Panama. 6 Laboratoire de Chimie de Coordination LCC-UPR 8241-CNRS, 31400 Toulouse, France. 7 Present Address: Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA. 8 Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA. 9 Division of Infectious Diseases, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA. 10 The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA. 11 Montpellier Cell Biology Research Center (CRBM), CNRS-UMR 5237 Université de Montpellier, Montpellier, France. 12 Center for Cooperative Research in Biosciences (CIC bioGUNE), Basque Research and Technology Alliance (BRTA), Bizkaia Technology Park, Building 801A, 48160 Derio, Spain. 13 Instituto Bio TecMed, Universitat de València, Burjassot, 46100 Valencia, Spain. 14 Departamento de Biología Molecular y Celular, Centro Nacional de Biotecnología (CNB), CSIC, Darwin 3, 28049 Madrid, Spain. 15 Present Address: Centro Andaluz de Biología Molecular y Medicina Regenerativa (CABIMER), C/ Américo Vespucio 24, Edificio Cabimer, 41092 Seville, Spain. 16 Present Address: Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, ON M5G 1X5, Canada. *Corresponding author: mcarmen.rivas@usc.es |
|
| Read full article at BMC | ||
| No. 16 | DOI: 10.1186/s11658-024-00534-4 Volume 29 (2024) - 29:16 | |
| Title | CORRECTION: ALKBH5 IN MOUSE TESTICULAR SERTOLI CELLS REGULATES Cdh2 mRNA TRANSLATION TO MAINTAIN BLOOD–TESTIS BARRIER INTEGRITY | |
| Authors | Zhonglin Cai1,2,3, Yao Zhang2, Lin Yang2, Chunhui Ma2, Yi Fei2, Jing Ding2, Wei Song4, Wei‐Min Tong2,5*, Yamei Niu2,5* and Hongjun Li1* | |
| Abstract |
Correction: Cellular & Molecular Biology Letters (2022) 27:101 https://doi.org/10.1186/s11658-022-00404-x Following publication of the original article [1], the authors corrected the Funding section. The incorrect Funding is: This work is supported by the Grant from National Natural Science Foundation of China (81871152, 82171588), National Key R&D Program of China (2019YFA080703), and Chinese Academy of Medical Sciences (CAMS) Initiative for Innovative Medicine (2021-I2M-1-002). The correct Funding is: This work is supported by the Grant from National Natural Science Foundation of China (81871152, 82171588), National Key R&D Program of China (2019YFA0801703), and Chinese Academy of Medical Sciences (CAMS) Initiative for Innovative Medicine (2021-I2M-1-002). | |
| Keywords | ||
| Address and Contact Information |
1 Department of Urology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China 2 Department of Pathology, Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Beijing, China 3 Department of Urology, Shanghai Ninth People’s Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China 4 Department of Biochemistry and Molecular Biology, State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Beijing, China 5 Molecular Pathology Research Center, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China *Corresponding author: wmtong@ibms.pumc.edu.cn; niuym@ibms.pumc.edu.cn; lihongjun@pumch.cn |
|
| Read full article at BMC | ||
| No. 17 | DOI: 10.1186/s11658-024-00535-3 Volume 29 (2024) - 29:17 | |
| Title | FFAR4 ACTIVATION INHIBITS LUNG ADENOCARCINOMA VIA BLOCKING RESPIRATORY CHAIN COMPLEX ASSEMBLY ASSOCIATED MITOCHONDRIAL METABOLISM | |
| Authors | Zhe Wang1†, Jinyou Li2†, LongFei Wang3†, Yaowei Liu4, Wei Wang1, JiaYao Chen1, HuiJun Liang1, Y. Q. Chen1 and ShengLong Zhu1* | |
| Abstract | Despite notable advancements in the investigation and management of lung adenocarcinoma (LUAD), the mortality rate for individuals afflicted with LUAD remains elevated, and attaining an accurate prognosis is challenging. LUAD exhibits intricate genetic and environmental components, and it is plausible that free fatty acid receptors (FFARs) may bridge the genetic and dietary aspects. The objective of this study is to ascertain whether a correlation exists between FFAR4, which functions as the primary receptor for dietary fatty acids, and various characteristics of LUAD, while also delving into the potential underlying mechanism. The findings of this study indicate a decrease in FFAR4 expression in LUAD, with a positive correlation (P < 0.01) between FFAR4 levels and overall patient survival (OS). Receiver operating characteristic (ROC) curve analysis demonstrated a significant diagnostic value [area under the curve (AUC) of 0.933] associated with FFAR4 expression. Functional investigations revealed that the FFAR4-specific agonist (TUG891) effectively suppressed cell proliferation and induced cell cycle arrest. Furthermore, FFAR4 activation resulted in significant metabolic shifts, including a decrease in oxygen consumption rate (OCR) and an increase in extracellular acidification rate (ECAR) in A549 cells. In detail, the activation of FFAR4 has been observed to impact the assembly process of the mitochondrial respiratory chain complex and the malate–aspartate shuttle process, resulting in a decrease in the transition of NAD+ to NADH and the inhibition of LUAD. These discoveries reveal a previously unrecognized function of FFAR4 in the negative regulation of mitochondrial metabolism and the inhibition of LUAD, indicating its potential as a promising therapeutic target for the treatment and diagnosis of LUAD. | |
| Keywords | FFAR4, LUAD, OXPHOS, Metabolism reprogramming | |
| Address and Contact Information |
1 Wuxi School of Medicine, Jiangnan University, Wuxi, China 2 Department of Thoracic Surgery, Affiliated Hospital of Jiangnan University, Wuxi, China 3 The First Affiliated Hospital of Ningbo University, Ningbo, China 4 State Key Lab of Food Science and Resources, Jiangnan University, Wuxi, China *Corresponding author: shenglongzhu@jiangnan.edu.cn † Zhe Wang, Jinyou Li, and LongFei Wang contributed equally to this work. |
|
| Read full article at BMC | ||
| No. 18 | DOI: 10.1186/s11658-024-00537-1 Volume 29 (2024) - 29:18 | |
| Title | PRO-INFLAMMATORY CYTOKINES STIMULATE CFTR-DEPENDENT ANION SECRETION IN PANCREATIC DUCTAL EPITHELIUM | |
| Authors | Dora Angyal1, Tessa A. Groeneweg1, Anny Leung1, Max Desain1, Kalyan Dulla2, Hugo R. de Jonge1^ and Marcel J. C. Bijvelds1* | |
| Abstract | Background:
Loss of CFTR-dependent anion and fluid secretion in the ducts of the exocrine pancreas is thought to contribute to the development of pancreatitis, but little is known about the impact of inflammation on ductal CFTR function. Here we used adult stem cell-derived cell cultures (organoids) obtained from porcine pancreas to evaluate the effects of pro-inflammatory cytokines on CFTR function. Methods: Organoids were cultured from porcine pancreas and used to prepare ductal epithelial monolayers. Monolayers were characterized by immunocytochemistry. Epithelial bicarbonate and chloride secretion, and the effect of IL-1β, IL-6, IFN-γ, and TNF-α on CFTR function was assessed by electrophysiology. Results: Immunolocalization of ductal markers, including CFTR, keratin 7, and zonula occludens 1, demonstrated that organoid-derived cells formed a highly polarized epithelium. Stimulation by secretin or VIP triggered CFTR-dependent anion secretion across epithelial monolayers, whereas purinergic receptor stimulation by UTP, elicited CFTR-independent anion secretion. Most of the anion secretory response was attributable to bicarbonate transport. The combination of IL-1β, IL-6, IFN-γ, and TNF-α markedly enhanced CFTR expression and anion secretion across ductal epithelial monolayers, whereas these cytokines had little effect when tested separately. Although TNF-α triggered apoptotic signaling, epithelial barrier function was not significantly affected by cytokine exposure. Conclusions: Pro-inflammatory cytokines enhance CFTR-dependent anion secretion across pancreatic ductal epithelium. We propose that up-regulation of CFTR in the early stages of the inflammatory response, may serve to promote the removal of pathogenic stimuli from the ductal tree, and limit tissue injury. | |
| Keywords | CFTR, Cystic fbrosis, Cytokines, Epithelial ion transport, Organoid, Pancreatitis | |
| Address and Contact Information |
1 Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center, PO Box 2040, 3000CA Rotterdam, The Netherlands 2 Boehringer Ingelheim Pharma GmbH & Co. KG, Binger Strasse 173, 55216 Ingelheim Am Rhein, Germany *Correspondence: m.bijvelds@erasmusmc.nl Hugo R. de Jonge: Deceased. |
|
| Read full article at BMC | ||
| No. 19 | DOI: 10.1186/s11658-024-00539-z Volume 29 (2024) - 29:19 | |
| Title | REGULATION OF TUMOR METASTASIS AND CD8+ T CELLS INFILTRATION BY circRNF216/miR-576-5p/ZC3H12C AXIS IN COLORECTAL CANCER | |
| Authors | Wenqi Du1,3,4†, Xin Quan1†, Chaoqun Wang1†, Qiuya Song1, Jie Mou2* and Dongsheng Pei1,4* | |
| Abstract | Background:
The tumor immune microenvironment (TIME) is an important regulator of tumor progression, growth and metastasis. In addition, tumor metastasis is one of the principal obstacles to the treatment of colorectal cancer (CRC). Circular RNAs (circRNAs) have been recognized as important regulators in the development of malignancies. However, their specific roles and mechanisms in both CRC metastasis and TIME have not been thoroughly investigated. Methods: High-throughput next-generation sequencing technology and real-time fluorescence quantitative PCR technology were performed to identify differential circRNAs in CRC. Functional assays including transwell assay, wound healing assay, and metastasis models were conducted to assess the effect of circRNF216 on CRC metastasis. In addition, luciferase reporter, western blot, RNA immunoprecipitation (RIP), and fluorescent in situ hybridization (FISH) were performed to explore the underlying mechanism of circRNF216. The level of immune infiltration was assessed by bioinformatics analysis and flow cytometry in CRC model. Furthermore, rescue and mutation experiments were used for verification. Results: circRNF216 was identified as a putative tumor suppressor that is downregulated in CRC tissues and cells. Overexpression of circRNF216 inhibits metastasis in vitro and vivo. Mechanistically, circRNF216 acts as a competitive endogenous RNA (ceRNA) for miR-576-5p, alleviating miR-576-5p repression on its target ZC3H12C, which in turn downregulated N-cadherin. Additionally, circRNF216 could enhance the infiltration level of CD8+ T cells by upregulating ZC3H12C, ultimately inhibiting the development of CRC, which suggests that circRNF216 is a potential biomarker for the treatment of CRC. Conclusions: Here, we provide novel mechanistic insight revealing how circRNF216 functioned in CRC metastasis and TIME via the circRNF216/miR-576-5p/ZC3H12C pathway. Therefore, circRNF216 holds promise as a potential therapeutic target and novel diagnostic marker for CRC. | |
| Keywords | Tumor immune microenvironment, Metastasis, Colorectal cancer, CircRNF216, MiR-576-5p, ZC3H12C | |
| Address and Contact Information |
1 Department of Pathology, Xuzhou Medical University, 209 Tongshan Road, Xuzhou, Jiangsu 221004, People’s Republic of China 2 School of Pharmacy, Xuzhou Medical University, Xuzhou, China 3 Department of Human Anatomy, Xuzhou Medical University, Xuzhou, China 4 Cancer Institute, Xuzhou Medical University, Xuzhou, China *Correspondence: mou.jie@xzhmu.edu.cn; dspei@xzhmu.edu.cn † Wenqi Du, Xin Quan and Chaoqun Wang contributed equally to this work. |
|
| Read full article at BMC | ||
| No. 20 | DOI: 10.1186/s11658-024-00532-6 Volume 29 (2024) - 29:20 | |
| Title | ROLE OF microRNA-4739 IN ENHANCING CISPLATIN CHEMOSENSITIVITY BY NEGATIVE REGULATION OF RHBDD2 IN HUMAN CERVICAL CANCER CELLS | |
| Authors | Yuling Li1, Zhengtong Zhou2, Jinfeng Qu1, Peiling Gong3, Yuyan Wei1 and Yaping Sun1* | |
| Abstract |
Background:
Cisplatin (DDP) is a widely used chemotherapy drug for advanced cervical cancer (CC), but resistance poses a significant challenge. While miR-4739 has been implicated in tumor development, its specific role in regulating DDP resistance in CC remains unclear. Methods: We analyzed the expression levels of miR-4739 and RHBDD2 in DDP-resistant and DDP-sensitive CC tissues using quantitative real-time polymerase chain reaction (PCR) and assessed their correlation through Spearman’s correlation analysis. DDP-resistant CC cell lines (HeLa/DDP and SiHa/DDP) were established by gradually increasing DDP concentrations, followed by transfection with miR-4739 mimics, si-RHBDD2, or a RHBDD2 overexpression vector. A series of functional assays, including CCK-8 assay, colony formation, flow cytometry, and transwell assay were performed. The interaction between miR-4739 and RHBDD2 was confirmed by luciferase reporter assay. We examined the protein levels of RHBDD2, P-gP, MRP1, cleaved caspase-3, and E-cadherin through western blot analysis. Moreover, we generated xenograft tumors by injecting stably transfected HeLa/DDP cells into mice to compare their tumorigenesis capacity. Results: We observed downregulation of miR-4739 and upregulation of RHBDD2 in DDP-resistant CC tissues and cell lines. MiR-4739 was shown to directly bind to RHBDD2 gene sequences to repress RHBDD2 expression in HeLa/DDP and SiHa/DDP cells. Our in vitro and in vivo experiments demonstrated that overexpressing miR-4739 overcame DDP resistance in CC cells by targeting RHBDD2. Furthermore, RHBDD2 overexpression reversed the effects of miR-4739 mimics on drug-resistance-related proteins (P-gP and MRP1) and the expression of cleaved caspase-3 and E-cadherin in HeLa/DDP cells. Conclusions: In summary, our study revealed that miR-4739 can reverse DDP resistance by modulating RHBDD2 in CC cells. | |
| Keywords | Cervical cancer, miR-4739, Cisplatin, Drug resistance, RHBDD2 | |
| Address and Contact Information |
1 Department of Gynecology, Central Hospital Affiliated to Shandong First Medical University, No.105, Jiefang Road, Lixia District, Jinan 250013, Shandong, China 2 Institute of Medical Genomics, Biomedical Sciences College & Shandong Medicinal Biotechnology Centre, Medical Science and Technology Innovation Center, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, Shandong, China 3 Yiyuan Maternal and Child Health Hospital, Zibo 256100, Shandong, China *Corresponding author: sun_yapingS78@yeah.net |
|
| Read full article at BMC | ||
| No. 21 | DOI: 10.1186/s11658-024-00536-2 Volume 29 (2024) - 29:21 | |
| Title | NEW INSIGHTS INTO THE ROLE OF MITOCHONDRIAL METABOLIC DYSREGULATION AND IMMUNE INFILTRATION IN SEPTIC CARDIOMYOPATHY BY INTEGRATED BIOINFORMATICS ANALYSIS AND EXPERIMENTAL VALIDATION | |
| Authors | Yukun Li1,2, Jiachi Yu3, Ruibing Li3, Hao Zhou1,3* and Xing Chang1,4* | |
| Abstract | Background:
Septic cardiomyopathy (SCM), a common cardiovascular comorbidity of sepsis, has emerged among the leading causes of death in patients with sepsis. SCM’s pathogenesis is strongly affected by mitochondrial metabolic dysregulation and immune infiltration disorder. However, the specific mechanisms and their intricate interactions in SCM remain unclear. This study employed bioinformatics analysis and drug discovery approaches to identify the regulatory molecules, distinct functions, and underlying interactions of mitochondrial metabolism and immune microenvironment, along with potential interventional strategies in SCM. Methods: GSE79962, GSE171546, and GSE167363 datasets were obtained from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) and module genes were identified using Limma and Weighted Correlation Network Analysis (WGCNA), followed by functional enrichment analysis. Machine learning algorithms, including support vector machine–recursive feature elimination (SVM–RFE), least absolute shrinkage and selection operator (LASSO) regression, and random forest, were used to screen mitochondria-related hub genes for early diagnosis of SCM. Subsequently, a nomogram was developed based on six hub genes. The immunological landscape was evaluated by single-sample gene set enrichment analysis (ssGSEA). We also explored the expression pattern of hub genes and distribution of mitochondria/inflammation-related pathways in UMAP plots of single-cell dataset. Potential drugs were explored using the Drug Signatures Database (DSigDB). In vivo and in vitro experiments were performed to validate the pathogenetic mechanism of SCM and the therapeutic efficacy of candidate drugs. Results: Six hub mitochondria-related DEGs [MitoDEGs; translocase of inner mitochondrial membrane domain-containing 1 (TIMMDC1), mitochondrial ribosomal protein S31 (MRPS31), F-box only protein 7 (FBXO7), phosphatidylglycerophosphate synthase 1 (PGS1), LYR motif containing 7 (LYRM7), and mitochondrial chaperone BCS1 (BCS1L)] were identified. The diagnostic nomogram model based on the six hub genes demonstrated high reliability and validity in both the training and validation sets. The immunological microenvironment differed between SCM and control groups. The Spearman correlation analysis revealed that hub MitoDEGs were significantly associated with the infiltration of immune cells. Upregulated hub genes showed remarkably high expression in the naive/memory B cell, CD14+ monocyte, and plasma cell subgroup, evidenced by the feature plot. The distribution of mitochondria/inflammation-related pathways varied across subgroups among control and SCM individuals. Metformin was predicted to be the most promising drug with the highest combined score. Its efficacy in restoring mitochondrial function and suppressing inflammatory responses has also been validated. Conclusions: This study presents a comprehensive mitochondrial metabolism and immune infiltration landscape in SCM, providing a potential novel direction for the pathogenesis and medical intervention of SCM. | |
| Keywords | Septic cardiomyopathy, Molecular mechanism, Drug discovery, Mitochondrial metabolism, Immune infltration | |
| Address and Contact Information |
1 Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing, China 2 National Clinical Research Center for Cardiovascular Diseases, Beijing, China 3 Department of Cardiology, The Sixth Medical Center of People’s Liberation Army General Hospital, Beijing, China 4 Guanganmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China *Corresponding author: zhouhao@plagh.org; xingchang_tcm@outlook.com |
|
| Read full article at BMC | ||
| No. 22 | DOI: 10.1186/s11658-023-00509-x Volume 29 (2024) - 29:22 | |
| Title | IP3R1-MEDIATED MAMs FORMATION CONTRIBUTES TO MECHANICAL TRAUMA-INDUCED HEPATIC INJURY AND THE PROTECTIVE EFFECT OF MELATONIN | |
| Authors | Rui Shi1,2,3†, Zhenhua Liu2†, Huan Yue2,4†, Man Li2,4, Simin Liu1, Dema De1,3, Runjing Li1,3, Yunan Chen1,3, Shuli Cheng5, Xiaoming Gu2, Min Jia2, Jun Li2, Juan Li2, Shumiao Zhang2, Na Feng2, Rong Fan2, Feng Fu2, Yali Liu2*, Mingge Ding1,5* and Jianming Pei2* | |
| Abstract | Introduction:
There is a high morbidity and mortality rate in mechanical trauma (MT)-induced hepatic injury. Currently, the molecular mechanisms underlying liver MT are largely unclear. Exploring the underlying mechanisms and developing safe and effective medicines to alleviate MT-induced hepatic injury is an urgent requirement. The aim of this study was to reveal the role of mitochondria-associated ER membranes (MAMs) in post-traumatic liver injury, and ascertain whether melatonin protects against MT-induced hepatic injury by regulating MAMs. Methods: Hepatic mechanical injury was established in Sprague–Dawley rats and primary hepatocytes. A variety of experimental methods were employed to assess the effects of melatonin on hepatic injury, apoptosis, MAMs formation, mitochondrial function and signaling pathways. Results: Significant increase of IP3R1 expression and MAMs formation were observed in MT-induced hepatic injury. Melatonin treatment at the dose of 30 mg/kg inhibited IP3R1-mediated MAMs and attenuated MT-induced liver injury in vivo. In vitro, primary hepatocytes cultured in 20% trauma serum (TS) for 12 h showed upregulated IP3R1 expression, increased MAMs formation and cell injury, which were suppressed by melatonin (100 μmol/L) treatment. Consequently, melatonin suppressed mitochondrial calcium overload, increased mitochondrial membrane potential and improved mitochondrial function under traumatic condition. Melatonin’s inhibitory effects on MAMs formation and mitochondrial calcium overload were blunted when IP3R1 was overexpressed. Mechanistically, melatonin bound to its receptor (MR) and increased the expression of phosphorylated ERK1/2, which interacted with FoxO1 and inhibited the activation of FoxO1 that bound to the IP3R1 promoter to inhibit MAMs formation. Conclusion: Melatonin prevents the formation of MAMs via the MR-ERK1/2-FoxO1-IP3R1 pathway, thereby alleviating the development of MT-induced liver injury. Melatonin-modulated MAMs may be a promising therapeutic therapy for traumatic hepatic injury. | |
| Keywords | Mechanical trauma, Melatonin, MAMs, ERK1/2, FoxO1, IP3R1 | |
| Address and Contact Information |
1 Department of Geriatrics Cardiology, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China 2 Department of Physiology and Pathophysiology, National Key Discipline of Cell Biology, Fourth Military Medical University, Xi’an, China 3 Key Laboratory of Surgical Critical Care and Life Support, Xi’an Jiaotong University, Ministry of Education, Xi’an, China 4 School of Life Science, Northwest University, Xi’an, China 5 The Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research, Laboratory Center of Stomatology, Department of Orthodontics, College of Stomatology, Xi’an Jiaotong University, Xi’an, China *Corresponding author: yaliliu@fmmu.edu.cn; dingmingge@xjtu.edu.cn; jmpei8@fmmu.edu.cn † Rui Shi, Zhenhua Liu and Huan Yue contributed equally to this study. |
|
| Read full article at BMC | ||
| No. 23 | DOI: 10.1186/s11658-024-00541-5 Volume 29 (2024) - 29:23 | |
| Title | UBIQUITOUS PROTEIN LACTYLATION IN HEALTH AND DISEASES | |
| Authors | Junyong Wang1,4†, Ziyi Wang1,4†, Qixu Wang1,4, Xiao Li3 and Yaping Guo1,2,4* | |
| Abstract | For decades, lactate has been considered a byproduct of glycolysis. The lactate shuttle hypothesis shifted the lactate paradigm, demonstrating that lactate not only plays important roles in cellular metabolism but also cellular communications, which can transcend compartment barriers and can occur within and among different cells, tissues and organs. Recently, the discovery that lactate can induce a novel post-translational modification, named lysine lactylation (Kla), brings forth a new avenue to study nonmetabolic functions for lactate, which has inspired a ‘gold rush’ of academic and commercial interest. Zhang et al. first showed that Kla is manifested in histones as epigenetic marks, and then mounting evidences demonstrated that Kla also occurs in diverse non-histone proteins. The widespread Kla faithfully orchestrates numerous biological processes, such as transcription, metabolism and inflammatory responses. Notably, dysregulation of Kla touches a myriad of pathological processes. In this review, we comprehensively reviewed and curated the existing literature to retrieve the new identified Kla sites on both histones and non-histone proteins and summarized recent major advances toward its regulatory mechanism. We also thoroughly investigated the function and underlying signaling pathway of Kla and comprehensively summarize how Kla regulates various biological processes in normal physiological states. In addition, we also further highlight the effects of Kla in the development of human diseases including inflammation response, tumorigenesis, cardiovascular and nervous system diseases and other complex diseases, which might potentially contribute to deeply understanding and interpreting the mechanism of its pathogenicity. | |
| Keywords | Glycolysis, Lactate, Lactylation, Pathological process | |
| Address and Contact Information |
1 Department of Pathophysiology, School of Basic Medical Sciences, Zhengzhou University, Science Avenue 100, Zhengzhou 450001, Henan, China 2 State Key Laboratory of Esophageal Cancer Prevention and Treatment, Zhengzhou 450001, Henan, China 3 Department of Gastroenterology, Henan Provincial People’s Hospital, Zhengzhou University People’s Hospital, Zhengzhou 450001, Henan, China 4 Center for Basic Medical Research, Academy of Medical Sciences, Zhengzhou University, Zhengzhou 450001, Henan, China *Corresponding author: guoyaping@zzu.edu.cn † Junyong Wang and Ziyi Wang equally contributed to this work. |
|
| Read full article at BMC | ||
| No. 24 | DOI: 10.1186/s11658-024-00542-4 Volume 29 (2024) - 29:24 | |
| Title | THE DIRECT BINDING OF BIOACTIVE PEPTIDE ANDERSONIN-W1 TO TLR4 EXPEDITES THE HEALING OF DIABETIC SKIN WOUNDS | |
| Authors | Chao Li3†, Yuxin Xiong1,4†, Zhe Fu1†, Yuxin Ji1, Jiayi Yan1, Yan Kong1, Ying Peng1, Zeqiong Ru1, Yubing Huang3, Yilin Li1, Ying Yang4*, Li He5*, Jing Tang3*, Ying Wang2* and Xinwang Yang1* | |
| Abstract | Background:
Chronic nonhealing wounds remain a considerable challenge in clinical treatment due to excessive inflammation and impeded reepithelialization and angiogenesis. Therefore, the discovery of novel prohealing agents for chronic skin wounds are urgent and important. Amphibian-derived prohealing peptides, especially immunomodulatory peptides, provide a promising strategy for the treatment of chronic skin trauma. However, the mechanism of immunomodulatory peptides accelerating the skin wound healing remains poorly understood. Methods: The prohealing ability of peptide Andersonin-W1 (AW1) was assessed by cell scratch, cell proliferation, transwell, and tube formation. Next, full-thickness, deep second-degree burns and diabetic full-thickness skin wounds in mice were performed to detect the therapeutic effects of AW1. Moreover, the tissue regeneration and expression of inflammatory cytokines were evaluated by hematoxylin and eosin (H&E), enzyme-linked immunosorbent assay (ELISA), and immunohistochemistry staining. Molecular docking, colocalization, and western blotting were used to explore the mechanism of AW1 in promoting wound healing. Results: We provide solid evidence to display excellent prohealing effects of AW1, identified as a short antimicrobial peptide in our previous report. At relative low concentration of nM, AW1 promoted the proliferation, migration, and scratch repair of keratinocyte, macrophage proliferation, and tube formation of HUVEC. AW1 also facilitated reepithelialization, granulation regeneration, and angiogenesis, thus significantly boosting the healing of full-thickness, deep second-degree burns and diabetic skin wounds in mice. Mechanistically, in macrophages, AW1 directly bound to Toll-like receptor 4 (TLR4) in the extracellular region and regulated the downstream nuclear factor‐κB (NF-κB) signaling pathway to facilitate the inflammatory factor secretion and suppress excessive inflammation induced by lipopolysaccharide (LPS). Moreover, AW1 regulated macrophage polarization to promote the transition from the inflammatory to the proliferative phase and then facilitated reepithelialization, granulation regeneration, and angiogenesis, thus exhibiting excellent therapeutic effects on diabetic skin wounds. Conclusions: AW1 modulates inflammation and the wound healing process by the TLR4/NF-κB molecular axis, thus facilitating reepithelialization, granulation regeneration, and angiogenesis. These findings not only provided a promising multifunctional prohealing drug candidate for chronic nonhealing skin wounds but also highlighted the unique roles of “small” peptides in the elucidation of “big” human disease mechanisms. | |
| Keywords | Diabetic skin wound healing, TLR4/NF-κB, Infammation, Angiogenesis | |
| Address and Contact Information |
1 Department of Anatomy and Histology and Embryology, Faculty of Basic Medical Science, Kunming Medical University, Kunming 650500, Yunnan, China 2 Key Laboratory of Chemistry in Ethnic Medicinal Resources and Key Laboratory of Natural Products Synthetic Biology of Ethnic Medicinal Endophytes, State Ethnic Affairs Commission and Ministry of Education, School of Ethnic Medicine, Yunnan Minzu University, Kunming 650504, Yunnan, China 3 Department of Biochemistry and Molecular Biology, Faculty of Basic Medical Science, Kunming Medical University, Kunming 650500, Yunnan, China 4 Department of Endocrinology, Affiliated Hospital of Yunnan University, Kunming 650021, Yunnan, China 5 Department of Dermatology, First Affiliated Hospital of Kunming Medical University, Kunming 650032, Yunnan, China *Correspondence: yangying2072@126.com; drheli2662@126.com; gracett916@163.com; wangying_814@163.com; yangxinwanghp@163.com; yangxinwang@kmmu.edu.cn † Chao Li, Yuxin Xiong, and Zhe Fu contributed equally to this manuscript. |
|
| Read full article at BMC | ||
| No. 25 | DOI: 10.1186/s11658-024-00540-6 Volume 29 (2024) - 29:25 | |
| Title | CircMAST1 INHIBITS CERVICAL CANCER PROGRESSION BY HINDERING THE N4-ACETYLCYTIDINE MODIFICATION OF YAP mRNA | |
| Authors | Chunyu Zhang1,2†, Li Yuan1,2†, Qiaojian Zou1,2†, Caixia Shao1,2, Yan Jia1,2, Jiaying Li1,2, Yan Liao1,2, Xueyuan Zhao1,2, Weijia Wen1,2, Xu Jing3, Guofen Yang1,2, Wei Wang1,2*, Hongye Jiang1,2* and Shuzhong Yao1,2* | |
| Abstract | Background:
Cervical cancer (CCa) is the fourth most common cancer among females, with high incidence and mortality rates. Circular RNAs (circRNAs) are key regulators of various biological processes in cancer. However, the biological role of circRNAs in cervical cancer (CCa) remains largely unknown. This study aimed to elucidate the role of circMAST1 in CCa. Methods: CircRNAs related to CCa progression were identified via a circRNA microarray. The relationship between circMAST1 levels and clinicopathological features of CCa was evaluated using the clinical specimens and data of 131 patients with CCa. In vivo and in vitro experiments, including xenograft animal models, cell proliferation assay, transwell assay, RNA pull-down assay, whole-transcriptome sequencing, RIP assay, and RNA-FISH, were performed to investigate the effects of circMAST1 on the malignant behavior of CCa. Results: CircMAST1 was significantly downregulated in CCa tissues, and low expression of CircMAST1 was correlated with a poor prognosis. Moreover, our results demonstrated that circMAST1 inhibited tumor growth and lymph node metastasis of CCa. Mechanistically, circMAST1 competitively sequestered N-acetyltransferase 10 (NAT10) and hindered Yes-associated protein (YAP) mRNA ac4C modification to promote its degradation and inhibit tumor progression in CCa. Conclusions: CircMAST1 plays a major suppressive role in the tumor growth and metastasis of CCa. In particular, circMAST1 can serve as a potential biomarker and novel target for CCa. | |
| Keywords | Cervical cancer, Circular RNA circMAST1, N4-acetylcytidine, NAT10, YAP | |
| Address and Contact Information |
1 Department of Obstetrics and Gynecology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China 2 Guangdong Provincial Clinical Research Center for Obstetrical and Gynecological Diseases, Guangzhou, China 3 Department of Microbiology, Tumor and Cell Biology, Karolinska Institute, Stockholm, Sweden *Corresponding author: wangw245@mail.sysu.edu.cn; jianghye@mail.sysu.edu.cn; yaoshuzh@mail.sysu.edu.cn † Chunyu Zhang, Li Yuan and Qiaojian Zou have contributed equally to this work. |
|
| Read full article at BMC | ||
| No. 26 | DOI: 10.1186/s11658-024-00544-2 Volume 29 (2024) - 29:26 | |
| Title | HIGH-CONTENT IMAGE SCREENING TO IDENTIFY CHEMICAL MODULATORS FOR PEROXISOME AND FERROPTOSIS | |
| Authors | Daheng Zheng1, Fei Li1, Shanshan Wang2, Pu‐Ste Liu3 and Xin Xie1* | |
| Abstract | Background:
The peroxisome is a dynamic organelle with variety in number, size, shape, and activity in different cell types and physiological states. Recent studies have implicated peroxisomal homeostasis in ferroptosis susceptibility. Here, we developed a U-2OS cell line with a fluorescent peroxisomal tag and screened a target-selective chemical library through high-content imaging analysis. Methods: U-2OS cells stably expressing the mOrange2-Peroxisomes2 tag were generated to screen a target-selective inhibitor library. The nuclear DNA was counterstained with Hoechst 33342 for cell cycle analysis. Cellular images were recorded and quantitatively analyzed through a high-content imaging platform. The effect of selected compounds on ferroptosis induction was analyzed in combination with ferroptosis inducers (RSL3 and erastin). Flow cytometry analysis was conducted to assess the level of reactive oxygen species (ROS) and cell death events. Results: Through the quantification of DNA content and peroxisomal signals in single cells, we demonstrated that peroxisomal abundance was closely linked with cell cycle progression and that peroxisomal biogenesis mainly occurred in the G1/S phase. We further identified compounds that positively and negatively regulated peroxisomal abundance without significantly affecting the cell cycle distribution. Some compounds promoted peroxisomal signals by inducing oxidative stress, while others regulated peroxisomal abundance independent of redox status. Importantly, compounds with peroxisome-enhancing activity potentiated ferroptosis induction. Conclusions: Our findings pinpoint novel cellular targets that might be involved in peroxisome homeostasis and indicate that compounds promoting peroxisomal abundance could be jointly applied with ferroptosis inducers to potentiate anticancer effect. | |
| Keywords | Peroxisome, Homeostasis, U-2OS, High-content screening, Ferroptosis, Oxidative stress, Target selective inhibitor | |
| Address and Contact Information |
1 School of Life and Environmental Sciences, Shaoxing University, Shaoxing City, Zhejiang, China 2 School of Life Sciences and Biopharmaceutics, Guangdong Pharmaceutical University, Guangdong, China 3 Department of Biochemistry and Molecular Biology, College of Medicine, National Cheng Kung University, Tainan, Taiwan, ROC *Corresponding author: 2022000032@usx.edu.cn |
|
| Read full article at BMC | ||
| No. 27 | DOI: 10.1186/s11658-024-00546-0 Volume 29 (2024) - 29:27 | |
| Title | THE ANCESTRAL TYPE OF THE R-RAS PROTEIN HAS ONCOGENIC POTENTIAL | |
| Authors | Antea Talajić1†, Kristina Dominko1†, Marija Lončarić2, Andreja Ambriović‐Ristov2 and Helena Ćetković1* | |
| Abstract | Background:
The R-RAS2 is a small GTPase highly similar to classical RAS proteins at the regulatory and signaling levels. The high evolutionary conservation of R-RAS2, its links to basic cellular processes and its role in cancer, make R-RAS2 an interesting research topic. To elucidate the evolutionary history of R-RAS proteins, we investigated and compared structural and functional properties of ancestral type R-RAS protein with human R-RAS2. Methods: Bioinformatics analysis were used to elucidate the evolution of R-RAS proteins. Intrinsic GTPase activity of purified human and sponge proteins was analyzed with GTPase-GloTM Assay kit. The cell model consisted of human breast cancer cell lines MCF-7 and MDA-MB-231 transiently transfected with EsuRRAS2-like or HsaRRAS2. Biological characterization of R-RAS2 proteins was performed by Western blot on whole cell lysates or cell adhesion protein isolates, immunofluorescence and confocal microscopy, MTT test, colony formation assay, wound healing and Boyden chamber migration assays. Results: We found that the single sponge R-RAS2-like gene/protein probably reflects the properties of the ancestral R-RAS protein that existed prior to duplications during the transition to Bilateria, and to Vertebrata. Biochemical characterization of sponge and human R-RAS2 showed that they have the same intrinsic GTPase activity and RNA binding properties. By testing cell proliferation, migration and colony forming efficiency in MDA-MB-231 human breast cancer cells, we showed that the ancestral type of the R-RAS protein, sponge R-RAS2-like, enhances their oncogenic potential, similar to human R-RAS2. In addition, sponge and human R-RAS2 were not found in focal adhesions, but both homologs play a role in their regulation by increasing talin1 and vinculin. Conclusions: This study suggests that the ancestor of all animals possessed an R-RAS2-like protein with oncogenic properties similar to evolutionarily more recent versions of the protein, even before the appearance of true tissue and the origin of tumors. Therefore, we have unraveled the evolutionary history of R-RAS2 in metazoans and improved our knowledge of R-RAS2 properties, including its structure, regulation and function. | |
| Keywords | Cancer, Cell migration, Cell proliferation, Evolution, Focal adhesion, Intracellular localization, Metazoa, R-RAS2, Small GTPase, Porifera | |
| Address and Contact Information |
1 Laboratory for Molecular Genetics, Division of Molecular Biology, Ruđer Bošković Institute, 10000 Zagreb, Croatia 2 Laboratory for Cell Biology and Signalling, Division of Molecular Biology, Ruđer Bošković Institute, 10000 Zagreb, Croatia *Corresponding author: Helena.Cetkovic@irb.hr † Antea Talajić and Kristina Dominko have contributed equally to this work. |
|
| Read full article at BMC | ||
| No. 28 | DOI: 10.1186/s11658-024-00543-3 Volume 29 (2024) - 29:28 | |
| Title | N6-METHYLADENOSINE-MODIFIED circ_104797 SUSTAINS CISPLATIN RESISTANCE IN BLADDER CANCER THROUGH ACTING AS RNA SPONGES | |
| Authors | Congjie Xu1†, Jiaquan Zhou1†, Xiaoting Zhang2†, Xinli Kang1, Shuan Liu1, Mi Song1, Cheng Chang1, Youtu Lin3 and Yang Wang1* | |
| Abstract | Background:
Bladder cancer (BCa) ranks among the predominant malignancies affecting the urinary system. Cisplatin (CDDP) remains a cornerstone therapeutic agent for BCa management. Recent insights suggest pivotal roles of circular RNA (circRNA) and N6-methyladenosine (m6A) in modulating CDDP resistance in BCa, emphasizing the importance of elucidating these pathways to optimize cisplatin-based treatments. Methods: Comprehensive bioinformatics assessments were undertaken to discern circ_104797 expression patterns, its specific interaction domains, and m6A motifs. These findings were subsequently corroborated through experimental validations. To ascertain the functional implications of circ_104797 in BCa metastasis, in vivo assays employing CRISPR/dCas13b-ALKBH5 were conducted. Techniques, such as RNA immunoprecipitation, biotin pull-down, RNA pull-down, luciferase reporter assays, and western blotting, were employed to delineate the underlying molecular intricacies. Results: Our investigations revealed an elevated expression of circ_104797 in CDDP-resistant BCa cells, underscoring its pivotal role in sustaining cisplatin resistance. Remarkably, demethylation of circ_104797 markedly augmented the potency of cisplatin-mediated apoptosis. The amplification of circ_104797 in CDDP-resistant cells was attributed to enhanced RNA stability, stemming from an augmented m6A level at a distinct adenosine within circ_104797. Delving deeper, we discerned that circ_104797 functioned as a microRNA reservoir, specifically sequestering miR-103a and miR-660-3p, thereby potentiating cisplatin resistance. Conclusions: Our findings unveil a previously uncharted mechanism underpinning cisplatin resistance and advocate the potential therapeutic targeting of circ_104797 in cisplatin-administered patients with BCa, offering a promising avenue for advanced BCa management. | |
| Keywords | Bladder cancer, Cisplatin resistance, circ_104797, miR-103a, N6-methyladenosine | |
| Address and Contact Information |
1 Department of Urology, Hainan General Hospital (Hainan Affiliated Hospital of Hainan Medical University), Haikou, Hainan, People’s Republic of China 2 Shenzhen Baoan District Songgang People’s Hospital, Shenzhen, Guangdong, People’s Republic of China 3 Department of Urology, The Third People’s Hospital of Danzhou, Danzhou, Hainan, People’s Republic of China *Corresponding author: Wysci2008@126.com † Congjie Xu, Jiaquan Zhou, and Xiaoting Zhang contributed equally to this work. |
|
| Read full article at BMC | ||