International Journal of Biological Sciences最新文献

{"title":"NDR1/FBXO11 promotes phosphorylation-mediated ubiquitination of β-catenin to suppress metastasis in prostate cancer","authors":"Zuodong Xuan, Chen Chen, Huimin Sun, Kunao Yang, Jinxin Li, Meilin Fu, Yang Bai, Zeyuan Zheng, Yue Zhao, Chunlan Xu, Bin Liu, Tian Li, Chen Shao","doi":"10.7150/ijbs.98907","DOIUrl":"https://doi.org/10.7150/ijbs.98907","url":null,"abstract":"<b>Background:</b> Prostate cancer progression hinges on β-catenin's stability and activity, a key factor in epithelial-mesenchymal transition (EMT) and metastasis. This study delves into NDR1-dependent phosphorylation's impact on β-catenin via FBXO11, an E3 ubiquitin ligase, in prostate cancer cells./n<b>Methods:</b> Human prostate cancer cell lines underwent various <i>in vitro</i> assays, including real-time PCR, Western blotting, immunoprecipitation, immunofluorescence, and protein stability assays, to explore β-catenin's interactions and post-translational modifications. NDR1 modulation's <i>in vivo</i> efficacy was assessed using a nude mice lung metastasis model. Small-molecule screening identified a potential NDR1 activator, aNDR1, tested for its effects on metastasis via <i>in vitro</i> and <i>in vivo</i> assays./n<b>Results:</b> NDR1 phosphorylated β-catenin at Ser33/37, facilitating its interaction with FBXO11. This led to FBXO11-mediated ubiquitination and cytoplasmic degradation of β-catenin, while the NDR1-FBXO11 complex impeded β-catenin nuclear translocation by inducing JNK2 ubiquitination. Thus, NDR1 and FBXO11 jointly regulate β-catenin activity in prostate cancer cells through dual phosphorylation-driven ubiquitination, potentially suppressing EMT. Reduced NDR1 expression inhibited FBXO11 and β-catenin phosphorylation, diminishing β-catenin and JNK2 ubiquitination, promoting EMT and enhancing prostate cancer cell metastasis. The inhibitory effects of aNDR1 on prostate cancer metastasis were validated./n<b>Conclusion:</b> The NDR1/FBXO11 axis outlines a non-canonical β-catenin degradation pathway crucial in regulating EMT and prostate cancer cell metastasis. NDR1 activation, particularly with aNDR1, could offer a promising therapeutic avenue against prostate cancer metastasis.","PeriodicalId":13762,"journal":{"name":"International Journal of Biological Sciences","volume":null,"pages":null},"PeriodicalIF":9.2,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142258115","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"RUNX1-MUC13 Interaction Activates Wnt/β-Catenin Signaling Implications for Colorectal Cancer Metastasis","authors":"Xinyi Chen, Jingyao Tu, Mu Yang, Yuan Wang, Bo Liu, Hong Qiu, Xianglin Yuan","doi":"10.7150/ijbs.98396","DOIUrl":"https://doi.org/10.7150/ijbs.98396","url":null,"abstract":"<b>Background:</b> Colorectal cancer (CRC) remains a significant global health challenge, often characterized by late-stage metastasis and poor prognosis. The Runt-related transcription factor 1 (RUNX1) plays a dual role as both an oncogene and a tumor suppressor in various cancers, including CRC. However, the specific regulatory mechanisms of RUNX1 in CRC, particularly its direct roles, are not fully understood./n<b>Objective:</b> This study aimed to investigate the role of RUNX1 in CRC progression and its interaction with Mucin 13 (MUC13) as a potential regulatory target./n<b>Methods:</b> RUNX1 expression was analyzed in CRC tissues and cell lines compared to controls. <i>In vitro</i> and <i>in vivo</i> assays were conducted to assess the effects of RUNX1 overexpression and knockdown on cell behavior. ChIP-seq and RNA-seq analyses were performed to identify RUNX1 targets, with a focus on MUC13./n<b>Results:</b> RUNX1 expression was significantly upregulated in CRC tissues and cells, correlating with advanced pathological characteristics and poor patient outcomes. RUNX1 overexpression enhanced CRC cell proliferation, migration, invasion, and G2/M phase arrest, while its knockdown had the opposite effects. MUC13 was identified as a direct transcriptional target of RUNX1, with its expression contributing to the activation of the Wnt/β-catenin signaling pathway. Disruption of MUC13 partially reversed the malignant phenotypes induced by RUNX1./n<b>Conclusion:</b> RUNX1 promotes CRC progression by upregulating MUC13 and activating the Wnt/β-catenin pathway. This RUNX1-MUC13 axis represents a potential therapeutic target for managing CRC.","PeriodicalId":13762,"journal":{"name":"International Journal of Biological Sciences","volume":null,"pages":null},"PeriodicalIF":9.2,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142258118","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"AFM41a: A Novel PAD2 Inhibitor for Sepsis Treatment-Efficacy and Mechanism.","authors":"Tao Dong, Leonard Barasa, Xin Yu, Wenlu Ouyang, Liujiazi Shao, Chao Quan, Su He Wang, Jifeng Zhang, Morgan Salmon, Allan Tsung, Hasan B Alam, Jianjie Ma, Paul R Thompson, Yongqing Li","doi":"10.7150/ijbs.97166","DOIUrl":"10.7150/ijbs.97166","url":null,"abstract":"<p><p><i>Pseudomonas aeruginosa</i> (PA) infection can cause pneumonia and sepsis by activating peptidyl-arginine deiminase (PAD) and triggering the formation of neutrophil extracellular traps (NETs). Our previous research has elucidated the crucial role of PAD2 in regulating CitH3 production and NETosis signaling following bacterial infection. Therefore, targeting PAD2 with selective inhibitors holds promise for treating PA-induced sepsis. Here, we compare the structure and function of two PAD2 inhibitors, AFM32a and AFM41a, and investigate their biological effects in mice subjected with PA. We analyze their impact on PAD2 inhibition, macrophage polarization, and other host defense mechanisms against PA-induced sepsis utilizing both <i>in vivo</i> and <i>in vitro</i> approaches. Our findings demonstrate that both PAD2 inhibitors (AFM32a and AFM41a) and <i>Pad2</i> deficiency substantially enhance protection against PA-induced sepsis, with AFM41a showing superior efficacy over AFM32a. This protective effect is marked by improved survival rates, reduced bacterial growth in mice subjected to PA infection, and the promotion of M2 macrophage polarization coupled with enhanced autophagic activity. Our results advocate for targeting PAD2 as an effective strategy to bolster host defenses against PA infection. Utilizing AFM41a to promote M2 macrophage polarization and autophagy offers promising avenues for the treatment of PA infection and the improvement of sepsis outcomes.</p>","PeriodicalId":13762,"journal":{"name":"International Journal of Biological Sciences","volume":null,"pages":null},"PeriodicalIF":8.2,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11488583/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142485689","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pharmacological manipulation of TRPC5 by kaempferol attenuates metastasis of gastrointestinal cancer via inhibiting calcium involved in the formation of filopodia","authors":"Suyun Yu, Rui Deng, Wei Wang, Defang Zou, Liang He, Zhonghong Wei, Yanhong Pan, Xiaoman Li, Yuanyuan Wu, Aiyun Wang, Wenxing Chen, Yang Zhao, Yin Lu","doi":"10.7150/ijbs.87829","DOIUrl":"https://doi.org/10.7150/ijbs.87829","url":null,"abstract":"The thermo-sensory receptor, transient receptor potential channel 5 (TRPC5), a non-selective calcium ion (Ca²⁺)-permeable ion channel, has been implicated in cancer initiation and progression. However, its specific role in gastrointestinal cancer remains unclear. This study demonstrates that TRPC5 is significantly overexpressed in gastrointestinal tumors and is inversely associated with patient prognosis. TRPC5 overexpression triggers a substantial elevation in intracellular Ca²⁺ levels ([Ca²⁺]i), driving actin cytoskeleton reorganization and facilitating filopodia formation. Furthermore, kaempferol, a compound sourced from traditional Chinese medicine, is identified as a TRPC5 inhibitor that effectively suppresses its activity, thereby impeding gastrointestinal cancer metastasis. These findings underscore the potential of TRPC5 as a therapeutic target for metastasis inhibition, with kaempferol emerging as a promising natural inhibitor that could be optimized for clinical use in preventing cancer metastasis.","PeriodicalId":13762,"journal":{"name":"International Journal of Biological Sciences","volume":null,"pages":null},"PeriodicalIF":9.2,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142258116","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Transcription Factor E2F4 Promote Proliferation, Migration, and Invasion of Gastric Cancer Cells by transcriptionally activating DSCC1","authors":"Shantanu Baral, Yantao Yu, Qiannan Sun, Mingrui Jiang, Ruiqi Li, Yifan Cheng, Arawker Mubeen Hussein, Youquan Shi, Yongjun Jiang, Dong Tang, Sen Wang, Daorong Wang","doi":"10.7150/ijbs.99590","DOIUrl":"https://doi.org/10.7150/ijbs.99590","url":null,"abstract":"Gastric cancer (GC) ranks as the fifth most common cancer and the fourth leading cause of cancer-related deaths globally. Despite advancements in molecular profiling, the mechanisms driving GC proliferation and metastasis remain unclear. This study identifies Early 2 Factor 4 (E2F4) as a key transcription factor that promotes GC cell proliferation, migration, and invasion by upregulating DNA Replication and Sister Chromatid Cohesion 1 (DSCC1) expression. Bioinformatics and transcription factor analyses revealed E2F4 as a significant regulator of DSCC1. Functional assays confirmed E2F4's role in enhancing GC cell malignancy <i>in vitro</i> and <i>in vivo</i>. Knockdown and overexpression experiments demonstrated that E2F4 positively regulates DSCC1 at the transcriptional level, with ChIP-qPCR and dual luciferase reporter assays validating the binding sites on the DSCC1 promoter. These findings highlight the E2F4-DSCC1 axis as a potential therapeutic target to mitigate GC progression.","PeriodicalId":13762,"journal":{"name":"International Journal of Biological Sciences","volume":null,"pages":null},"PeriodicalIF":9.2,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142258117","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Single-Cell RNA-Sequencing Identifies Bone Marrow-Derived Progenitor Cells as a Main Source of Extracellular Matrix-Producing Cells Across Multiple Organ-Based Fibrotic Diseases.","authors":"Yu Zhong, Biao Wei, Wenbiao Wang, Junzhe Chen, Wenjing Wu, Liying Liang, Xiao-Ru Huang, Cheuk-Chun Szeto, Xueqing Yu, David J Nikolic-Paterson, Hui-Yao Lan","doi":"10.7150/ijbs.98839","DOIUrl":"10.7150/ijbs.98839","url":null,"abstract":"<p><p>Fibrosis is characterized by the aberrant deposition of extracellular matrix (ECM) due to dysregulated tissue repair responses, imposing a significant global burden on fibrosis-related diseases. Although alpha-smooth muscle actin (α-SMA/<i>ACTA2</i>)-expressing myofibroblasts are considered as key player in fibrogenesis, the origin of ECM-producing cells remains controversial. To address this issue, we integrated and analyzed large-scale single-cell transcriptomic datasets from patients with distinct fibrotic diseases involving the heart, lung, liver, or kidney. Unexpectedly, not all <i>ACTA2-</i>expressing cells were ECM-producing cells identified by expressing collagen genes; instead, the majority of ECM-producing cells were myofibroblasts and fibroblasts derived from circulating bone marrow precursor, and to a lesser extent from local pericytes and vascular smooth cells in all fibrotic diseases. This was confirmed in sex-mismatched kidney transplants by the discovery that ECM-producing cells originated from recipient, not donor, bone marrow-derived progenitor cells (BMPCs). Moreover, these BMPCs-derived ECM-producing cells exhibited a proinflammatory phenotype. Thus, bone marrow-derived proinflammatory and profibrotic fibroblasts/myofibroblasts with stem cell properties serve as a major source of ECM-producing cells and may play a driving role in tissue fibrosis across a wide range of human fibrotic diseases. Targeting these ECM-producing cells may provide a novel therapy for diseases with fibrosis.</p>","PeriodicalId":13762,"journal":{"name":"International Journal of Biological Sciences","volume":null,"pages":null},"PeriodicalIF":8.2,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11488580/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142464523","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ESM1 facilitates the EGFR/HER3-triggered epithelial-to-mesenchymal transition and progression of gastric cancer via modulating interplay between Akt and angiopoietin-2 signaling","authors":"Yi-Chieh Yang, Ko-Hao Ho, Ke-Fan Pan, Kuo-Tai Hua, Min-Che Tung, Chia-Chi Ku, Ji-Qing Chen, Michael Hsiao, Chi-Long Chen, Wei-Jiunn Lee, Ming-Hsien Chien","doi":"10.7150/ijbs.100276","DOIUrl":"https://doi.org/10.7150/ijbs.100276","url":null,"abstract":"Gastric cancer (GC) poses global challenges due to its difficult early diagnosis and drug resistance, necessitating the identification of early detection markers and understanding of oncogenic pathways for effective GC therapy. Endothelial cell-specific molecule 1 (ESM1), a secreted glycoprotein, is elevated in various cancers, but its role in GC remains controversial. In our study, ESM1 was elevated in GC tissues, and its concentration was correlated with progression and poorer patient prognosis in independent cohorts. Functionally, ESM1 expression promoted proliferation, anoikis resistance, and motility of GC cells, as well as tumor growth in PDOs and in GC xenograft models. Mechanistically, ESM1 expression triggered the epithelial-to-mesenchymal transition (EMT) of GC cells by enhancing epidermal growth factor receptor (EGFR)/human EGFR 3 (HER3) association and activating the EGFR/HER3-Akt pathway. Additionally, angiopoietin-2 (ANGPT2) was found to be highly correlated with ESM1 and interplayed with Akt to induce the EMT and cancer progression. Use of a signal peptide deletion mutant (ESM1-19del) showed that the secreted form of ESM1 is crucial for its protumorigenic effects by activating the EGFR/HER3-Akt/ANGPT2 pathway to promote the EMT. Patients with high levels of both ESM1 and ANGPT2 had the poorest prognoses. Furthermore, therapeutic peptides successfully inhibited ESM1's induction of the aforementioned signals and motility of GC cells. ESM1's oncogenic role in GC involves activating the EGFR/HER3-Akt/ANGPT2 pathway, presenting a potential therapeutic target for GC.","PeriodicalId":13762,"journal":{"name":"International Journal of Biological Sciences","volume":null,"pages":null},"PeriodicalIF":9.2,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142258120","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bridging Chronic Inflammation and Digestive Cancer: The Critical Role of Innate Lymphoid Cells in Tumor Microenvironments","authors":"Guanliang Shen, Qi Wang, Zhengrui Li, Jiaheng Xie, Xinda Han, Zehao Wei, Pengpeng Zhang, Songyun Zhao, Xiumei Wang, Xufeng Huang, Min Xu","doi":"10.7150/ijbs.96338","DOIUrl":"https://doi.org/10.7150/ijbs.96338","url":null,"abstract":"The incidence and mortality of digestive system-related cancers have always been high and attributed to the heterogeneity and complexity of the immune microenvironment of the digestive system. Furthermore, several studies have shown that chronic inflammation in the digestive system is responsible for cancer incidence; therefore, controlling inflammation is a potential strategy to stop the development of cancer. Innate Lymphoid Cells (ILC) represent a heterogeneous group of lymphocytes that exist in contrast to T cells. They function by interacting with cytokines and immune cells in an antigen-independent manner. In the digestive system cancer, from the inflammatory phase to the development, migration, and metastasis of tumors, ILC have been found to interact with the immune microenvironment and either control or promote these processes. The conventional treatments for digestive tumors have limited efficacy, therefore, ILC-associated immunotherapies are promising strategies. This study reviews the characterization of different ILC subpopulations, how they interact with and influence the immune microenvironment as well as chronic inflammation, and their promotional or inhibitory role in four common digestive system tumors, including pancreatic, colorectal, gastric, and hepatocellular cancers. In particular, the review emphasizes the role of ILC in associating chronic inflammation with cancer and the potential for enhanced immunotherapy with cytokine therapy and adoptive immune cell therapy.","PeriodicalId":13762,"journal":{"name":"International Journal of Biological Sciences","volume":null,"pages":null},"PeriodicalIF":9.2,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142258174","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mechanisms of hepatic and renal injury in lipid metabolism disorders in metabolic syndrome","authors":"Jin Rong, Zixuan Zhang, Xiaoyu Peng, Ping Li, Tingting Zhao, Yifei Zhong","doi":"10.7150/ijbs.100394","DOIUrl":"https://doi.org/10.7150/ijbs.100394","url":null,"abstract":"Metabolic syndrome (MetS) is a group of metabolic abnormalities that identifies people at risk for diabetes and cardiovascular disease. MetS is characterized by lipid disorders, and non-alcoholic fatty liver disease (NAFLD) and diabetic kidney disease (DKD) are thought to be the common hepatic and renal manifestations of MetS following abnormal lipid metabolism. This paper reviews the molecular mechanisms of lipid deposition in NAFLD and DKD, highlighting the commonalities and differences in lipid metabolic pathways in NAFLD and DKD. Hepatic and renal steatosis is the result of lipid acquisition exceeding lipid processing, i.e., fatty acid uptake and lipid regeneration exceed fatty acid oxidation and export. This process is directly regulated by the interactions of nuclear receptors, transporter proteins and transcription factors, whereas pathways such as oxidative stress, autophagy, cellular pyroptosis and gut flora are also key regulatory hubs for lipid metabolic homeostasis but act slightly differently in the liver and kidney. Such insights based on liver-kidney similarities and differences offer potential options for improved treatment.","PeriodicalId":13762,"journal":{"name":"International Journal of Biological Sciences","volume":null,"pages":null},"PeriodicalIF":9.2,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142258122","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"METTL3-mediated m6A modification of OTUD1 aggravates press overload induced myocardial hypertrophy by deubiquitinating PGAM5","authors":"Kai Huang, Xiaotian Sun, Xiangyang Xu, Jie Lu, Boyao Zhang, Qin Li, Chuyi Wang, Sufan Ding, Xiaolei Huang, Xiaohong Liu, Zhiyun Xu, Lin Han","doi":"10.7150/ijbs.95707","DOIUrl":"https://doi.org/10.7150/ijbs.95707","url":null,"abstract":"<b>Background</b>: Pathological cardiac hypertrophy, a condition that contributes to heart failure, is characterized by its intricate pathogenesis. The meticulous regulation of protein function, localization, and degradation is a crucial role played by deubiquitinating enzymes in cardiac pathophysiology. This study clarifies the participation and molecular mechanism of OTUD1 (OTU Deubiquitinase 1) in pathological cardiac hypertrophy./n<b>Methods</b>: We generated a cardiac-specific Otud1 knockout mouse line (Otud1-CKO) and adeno-associated virus serotype 9-Otud1 mice to determine the role of Otud1 in cardiac hypertrophy. Its impact on cardiomyocytes enlargement was investigated using the adenovirus. RNA immunoprecipitation was used to validate the specific m6a methyltransferase interacted with OTUD1 transcript. RNA sequencing in conjunction with immunoprecipitation-mass spectrometry analysis was employed to identify the direct targets of OTUD1. A series of depletion mutant plasmids were constructed to detect the interaction domain of OTUD1 and its targets./n<b>Results</b>: Ang II-stimulated neonatal rat cardiac myocytes and mice hearts subjected to transverse aortic constriction (TAC) showed increased protein levels of Otud1. Cardiac hypertrophy and dysfunction were less frequent in Otud1-CKO mice during TAC treatment, while Otud1 overexpression worsened cardiac hypertrophy and remodeling. METTL3 mediated m6A modification of OTUD1 transcript promoted mRNA stability and elevated protein expression. In terms of pathogenesis, Otud1 plays a crucial role in cardiac hypertrophy by targeting Pgam5, leading to the robust activation of the Ask1-p38/JNK signal pathway to accelerate cardiac hypertrophy. Significantly, the pro-hypertrophy effects of Otud1 overexpression were largely eliminated when Ask1 knockdown./n<b>Conclusion</b>: Our findings confirm that targeting the OTUD1-PGAM5 axis holds significant potential as a therapeutic approach for heart failure associated with pathological hypertrophy./n/n\u0000","PeriodicalId":13762,"journal":{"name":"International Journal of Biological Sciences","volume":null,"pages":null},"PeriodicalIF":9.2,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142258123","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}