Cellular & Molecular Biology Letters最新文献

{"title":"EIF4A3-induced circUBAC2 promotes lung cancer progression via regulation of the Hippo signaling pathway.","authors":"Fan Meng, Xiaokang Zhang, Xinlin Wang, Binqiang Qiu, Dingcheng Zeng, Xiao Huang, Jianping Liu, Haiwu Wu, Kaiwang Cui, Bin Zhong, Weiyou Liu, Xiangwen Gong, Xin He","doi":"10.1186/s11658-026-00912-0","DOIUrl":"10.1186/s11658-026-00912-0","url":null,"abstract":"<p><p>BACKGROUND: Circular RNAs (circRNAs) are stable noncoding RNAs involved in cancer, yet their mechanisms in lung adenocarcinoma (LUAD) remain unclear. This study explores the oncogenic role of circUBAC2 in LUAD progression. METHODS: Differentially expressed circRNAs were screened by microarray. circUBAC2 expression/location was analyzed via quantitative real-time PCR (qRT-PCR), RNA in situ hybridization (RNA-ISH), and fluorescence in situ hybridization. Functional impacts were evaluated through wound healing, Transwell, EdU, colony formation, and xenograft models. circUBAC2 targets were identified by RNA-sequencing/proteomics, with protein interactions assessed via western blotting, immunoprecipitation, and ubiquitination assays. Molecular interactions were examined using dual luciferase, chromatin Immunoprecipitation (ChIP), and RNA pull-down. RESULTS: circUBAC2 was upregulated in LUAD tissues and correlated with poor prognosis. It promoted LUAD cell proliferation, migration, and invasion in vitro, as well as tumor growth/metastasis in vivo. Mechanistically, circUBAC2 competitively bound 14-3-3 to release YAP for nuclear translocation while scaffolding OTUB1–YAP interactions to enhance YAP deubiquitination and stabilization, collectively activating TEAD-mediated oncogenic transcription. EIF4A3 facilitated circUBAC2 biogenesis by binding flanking intronic regions. CONCLUSIONS: circUBAC2 drives LUAD progression via YAP signaling, positioning it as a therapeutic target and prognostic biomarker. </p>","PeriodicalId":9688,"journal":{"name":"Cellular & Molecular Biology Letters","volume":" ","pages":""},"PeriodicalIF":12.2,"publicationDate":"2026-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13277127/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147621946","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A tRNA-derived fragment tRF3019a promotes LUAD metastasis by stabilizing hnRNPK and enhancing MYH11 expression.","authors":"Xin Li, Weifang Cui, Zhangjie Wang, Danyao Chen, Zhenyu Kuang, Junjie Jiang, Yuwei Lai, Xiongzhou Zhang, Chaojun Duan, Chunfang Zhang, Xizhe Li","doi":"10.1186/s11658-026-00916-w","DOIUrl":"10.1186/s11658-026-00916-w","url":null,"abstract":"<p><p>BACKGROUND: tRNA-derived fragments (tRFs) have been shown to play important regulatory roles in cancer biology. However, the impact of tRFs on lung adenocarcinoma (LUAD) remains largely unexplored. METHODS: The differential expression of tRF3019a, a tRNA fragment derived from tRNA-Ala (AGC), was identified through database mining and subsequently validated by quantitative reverse transcription PCR (qRT–PCR) in pathological tissues obtained from 100 patients with LUAD. The role of tRF3019a in LUAD metastasis was assessed through both in vitro and in vivo experiments. A comprehensive investigation of its regulatory function involved RNA pulldown assays, mass spectrometry, RNA immunoprecipitation (RIP), western blotting, chromatin immunoprecipitation (ChIP), co-immunoprecipitation (Co-IP), and rescue assays. RESULTS: tRF3019a expression was significantly elevated in LUAD tumor tissues and was associated with advanced disease stage and metastatic progression. Higher tRF3019a expression correlated with shorter overall survival and disease-free survival. Functionally, tRF3019a enhanced LUAD cell migration and invasion both in vitro and in vivo. Mechanistically, tRF3019a interacted with heterogeneous nuclear ribonucleoprotein K (hnRNPK) and inhibited its ubiquitin-mediated proteasomal degradation, leading to increased hnRNPK protein stability. This was accompanied by changes in epithelial–mesenchymal transition (EMT)-associated markers, including increased N-cadherin and vimentin and decreased E-cadherin. Furthermore, tRF3019a enhanced hnRNPK-associated transcriptional regulation of the myosin heavy chain 11 (MYH11) gene, contributing to the pro-metastatic phenotype of LUAD cells. CONCLUSIONS: tRF3019a promotes LUAD progression and metastasis by stabilizing hnRNPK and enhancing hnRNPK-associated transcriptional regulation of MYH11. These findings identify a previously unrecognized tRF3019a–hnRNPK–MYH11 regulatory axis involved in LUAD metastasis. </p>","PeriodicalId":9688,"journal":{"name":"Cellular & Molecular Biology Letters","volume":" ","pages":""},"PeriodicalIF":12.2,"publicationDate":"2026-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13277126/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147621890","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrated analysis of single-cell RNA sequencing, transcriptomics, and thermal proteome profiling identifies PLCG1 as the therapeutic target of isopimpinellin in treating rheumatoid arthritis.","authors":"Huantian Cui, Ning Wang, Feitian Min, Huan Pei, Yuming Wang, Hanzhou Li, Qianqian Wan, Yan Meng, Mingwei He, Xiaoman Lv, Liwei Xing, Zixuan Li, Tianze Pan, Renlin Li, Weibo Wen, Xiangying Kong, Yuhong Bian","doi":"10.1186/s11658-026-00918-8","DOIUrl":"10.1186/s11658-026-00918-8","url":null,"abstract":"<p><p>BACKGROUND: Isopimpinellin (ISOP), derived from Toddalia asiatica (L.) Lam, is thought to possess anti-inflammatory potential. However, the effects of ISOP on rheumatoid arthritis (RA) and corresponding mechanisms remain unclear. METHODS: We evaluated the therapeutic effect of ISOP on RA using the collagen-induced arthritis (CIA) rat model. Subsequently, we determined the potential mechanisms of ISOP by combining single-cell RNA sequencing of rat synovial tissue in vivo with transcriptome analysis of macrophages in vitro. Molecular docking, thermal proteome profiling, cellular thermal shift assays, and drug affinity responsive target stability were then employed to identify the molecular targets of ISOP. Finally, we validated this target and explored the interaction between macrophages and RA-fibroblast-like synoviocytes (FLS) in vitro. RESULTS: We found that ISOP improved pathological changes in CIA rats. Mechanistically, ISOP inhibited macrophage migration and M1 macrophage polarization, and downregulated Spp1 expression. Furthermore, ISOP restrained the RAS/ERK pathway in M1 macrophages. Importantly, PLCG1 is a direct target of ISOP. Silencing PLCG1 reduced the related inhibitory effects of ISOP on M1 macrophage polarization. In addition, the supernatant of macrophages treated with ISOP reduced the proliferation and activation of RA-FLS. Silencing PLCG1 eliminated the regulatory effects of ISOP in the macrophage-RA-FLS co-culture system. CONCLUSIONS: ISOP exerts its anti-RA effects by targeting PLCG1 to inhibit the production of SPP1 in M1 macrophages. </p>","PeriodicalId":9688,"journal":{"name":"Cellular & Molecular Biology Letters","volume":" ","pages":""},"PeriodicalIF":12.2,"publicationDate":"2026-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13281331/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147618311","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ADAM9 in tumor biology: molecular functions, clinical implications, and therapeutic targeting.","authors":"Kuo-Hao Ho, Chao-Jung Wu, Yi-Chieh Yang, Ming-Hsien Chien","doi":"10.1186/s11658-026-00910-2","DOIUrl":"10.1186/s11658-026-00910-2","url":null,"abstract":"<p><p>A disintegrin and metalloproteinase 9 (ADAM9), a member of the ADAM family, is expressed across multiple organs and is crucial to multiple physiological processes. Increasing evidence implicates ADAM9 in cancer progression through extracellular matrix (ECM) remodeling, protein shedding, and tumor microenvironment modulation. This study comprehensively reviews the literature on the clinical significance of ADAM9 and the mechanistic roles of ADAM9 in cancer. The results of our pan-cancer analysis demonstrated that ADAM9 is frequently upregulated and consistently associated with poor prognosis across tumor types. The results of in silico analyses also revealed that increased ADAM9 expression is correlated with an immunosuppressive tumor microenvironment and the activation of cancer-promoting pathways, such as cell cycle progression, epithelial-mesenchymal transition (EMT), and metabolism. This study also reviewed therapeutic strategies targeting ADAM9 and evaluated their potential in cancer treatment. This review provides insights into ADAM9 as both a biomarker of malignancy and a promising therapeutic target.</p>","PeriodicalId":9688,"journal":{"name":"Cellular & Molecular Biology Letters","volume":" ","pages":""},"PeriodicalIF":12.2,"publicationDate":"2026-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13173819/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147615857","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"DYRK2 drives renal fibrosis through CDK1-dependent G2/M phase dysregulation in tubular epithelial cells.","authors":"Fang Bai, Chunjie Wang, Sha Wang, Yuxuan Zhao, Feng Feng, Kuipeng Yu, Lei Liu, Xiangdong Yang","doi":"10.1186/s11658-026-00917-9","DOIUrl":"10.1186/s11658-026-00917-9","url":null,"abstract":"<p><p>BACKGROUND: Renal fibrosis is a common pathological characteristic of chronic kidney disease (CKD) and serves as the critical prognostic indicator for renal outcomes. However, current therapeutic strategies for managing renal fibrosis remain limited. Dual-specificity tyrosine-phosphorylation-regulated kinase 2 (DYRK2), an evolutionarily conserved kinase, is implicated in cell proliferation and apoptosis in various pathological contexts. However, its role in renal fibrosis is unclear. METHODS: The expression of DYRK2 and association with renal injury and fibrosis were assessed in pathological sections from various CKD subtypes. Two independent renal fibrosis models, namely unilateral ureteral obstruction-induced and aristolochic acid-induced mice, were used to investigate the role of DYRK2 in renal fibrosis. Integrated multi-omics approaches, including RNA sequencing (RNA-seq) and liquid chromatography-tandem mass spectrometry (LC–MS/MS) interactomics, were employed to elucidate the underlying mechanisms. RESULTS: Clinically, DYRK2 expression was elevated in patients with CKD and strongly correlated with histopathological fibrosis, glomerular filtration rate (GFR) decline, and an increased urine albumin-to-creatine ratio (UACR) in patients. In experimental fibrosis models, DYRK2 expression was markedly upregulated, which was particularly observed in proximal tubules. Silencing DYRK2 attenuated tubular injury, collagen deposition, and fibroblast activation. RNA sequencing revealed significant enrichment of oxidative stress-related pathways upon DYRK2 silencing. Functional studies demonstrated that DYRK2 ablation restored redox homeostasis in renal tubular epithelial cells (RTECs). Moreover, Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment showed that DYRK2 ablation restored the G2/M phase of the cell cycle in RTECs, reflected by a decrease in the cyclin B1/cyclin D1 ratio, as well as reduced levels of p21 and phosphorylated histone H3 (P-H3). Mechanistically, mass spectrometry screening and co-immunoprecipitation assays revealed an interaction of DYRK2 and cyclin-dependent kinase 1 (CDK1). Notably, DYRK2 promoted phosphorylation of CDK1 at the Thr14 site, thereby inhibiting its activity. The increased Thr14 phosphorylation of CDK1 almost reversed the protective effects of DYRK2 loss on transforming growth factor (TGF)-β1-induced tubular cell injury and fibrosis. CONCLUSION: These findings highlight the pivotal role of DYRK2 in driving G2/M dysregulation in RTECs under fibrotic conditions. Targeting DYRK2 may offer a promising and novel therapeutic strategy for renal fibrosis. </p>","PeriodicalId":9688,"journal":{"name":"Cellular & Molecular Biology Letters","volume":" ","pages":""},"PeriodicalIF":12.2,"publicationDate":"2026-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13173717/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147615928","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ribbon constrains dendritic pruning via actin scaffolding and exocyst complex.","authors":"Wanting Wang, Su Wang, Yuhao Yuan, Menglong Rui","doi":"10.1186/s11658-026-00903-1","DOIUrl":"10.1186/s11658-026-00903-1","url":null,"abstract":"<p><p>BACKGROUND: During animal development, neurons selectively remove superfluous synaptic connections, strengthen key synapses, and optimize neural circuits in the brain, which is a core mechanism for fine-tuning the development of the nervous system. Drosophila class IV dendritic arborization (C4da) sensory neurons undergo dendrite-specific pruning during development. Nevertheless, the cell-autonomous inhibitory mechanisms of dendritic pruning in C4da neurons are largely unknown. METHODS AND RESULTS: Here, we discovered Ribbon (Rib), a nuclear BTB-domain protein, whose malfunction in C4da neurons causes a precocious occurrence of dendritic pruning. Our study further shows that the regulation of dendritic pruning by Rib is dependent on Akt/Tor signaling. Moreover, actin polymerization factors and exocyst complex subunits are also involved in repressing dendritic pruning and function as downstream effectors of Rib and Akt/Tor signaling. CONCLUSIONS: Overall, the present study reveals a cell-autonomous inhibitory mechanism of Rib in dendritic pruning, with a perspective to provide new insights into neurodevelopment and the pathogenesis of relevant neurological disorders. </p>","PeriodicalId":9688,"journal":{"name":"Cellular & Molecular Biology Letters","volume":" ","pages":""},"PeriodicalIF":12.2,"publicationDate":"2026-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13169544/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147608169","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Palmitoylation-dependent regulation of innate and adaptive immunity: molecular insights and translational opportunities.","authors":"Binhui Zhou, Bowen Zhang, Yingcheng Qi, Sainan Li, Tingting Liu, Tong Li, Ying Wang, Haifeng Wang, Jiaqi Lu, Fei Cao, Xiaohong Kang, Eryan Kong, Yinming Liang","doi":"10.1186/s11658-026-00904-0","DOIUrl":"10.1186/s11658-026-00904-0","url":null,"abstract":"<p><p>Immune cells orchestrate organismal defense through pathogen surveillance, tissue homeostasis, and immune tolerance, with innate and adaptive subsets coordinating context-specific responses. The dynamic lipid modification, S-palmitoylation (often referred to simply as palmitoylation), regulates membrane trafficking, signal transduction, and protein–protein interactions by spatiotemporally controlling the localization, stability, and activity of immune mediators. Dysregulation of this process in immune cells contributes to pathologies including immunosuppression, chronic inflammation, and autoimmunity. This review synthesizes current knowledge on how palmitoylation governs immune cell development, subset-specific functions, and immune-mediated pathologies—encompassing metabolic disorders, infectious diseases, autoimmune disorders, and cancer. We further explore the diagnostic and therapeutic potential of targeting palmitoyltransferases, depalmitoylases, and palmitoylation-dependent immune checkpoints to restore immune equilibrium. By integrating mechanistic insights into palmitoylation-dependent immune regulation with translational applications, this work underscores the potential of palmitoylation-centric biomarkers and therapies to transform immunological diagnostics and treatment.</p>","PeriodicalId":9688,"journal":{"name":"Cellular & Molecular Biology Letters","volume":" ","pages":""},"PeriodicalIF":12.2,"publicationDate":"2026-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13270668/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147608204","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting mutant p53 in cancer: from mechanistic insights to therapeutic strategies.","authors":"H Helena Wu, Sarah Leng, David D Eisenstat, Consolato Sergi, Roger Leng","doi":"10.1186/s11658-026-00907-x","DOIUrl":"10.1186/s11658-026-00907-x","url":null,"abstract":"<p><p>The tumor suppressor p53, often referred to as the “guardian of the genome,” is mutated in more than half of human cancers. These mutations have a significant impact on cancer biology and response to therapy. p53 mutations involve a range of changes that interfere with DNA binding, eliminate tumor suppressor functions, and, in many cases, confer dominant-negative or gain-of-function characteristics that actively promote oncogenesis. These mutations are closely linked to poor clinical outcomes and resistance to standard treatments. This review examines the impact of p53 mutations on cancer therapy in various ways. In chemotherapy and radiotherapy, loss of wild-type p53 impairs DNA damage responses, whereas mutant forms often contribute to treatment resistance. Additionally, p53 status influences responses to targeted therapies and immunotherapies, thereby affecting patient outcomes and prognoses. Importantly, ongoing clinical trials are beginning to integrate p53 mutational status as a predictive biomarker for therapy selection. Strategies aimed at restoring p53 activity are gaining increasing popularity in the development of treatments. These approaches include gene therapy to reintroduce the wild-type gene, targeted degradation of mutant p53 proteins, and small molecules designed to refold or reactivate mutant p53. In addition, synthetic lethality frameworks are being utilized to exploit vulnerabilities specific to tumors with p53 mutations, as well as interventions that target downstream effectors of p53 pathway. Together, these strategies represent a significant shift in precision oncology.</p>","PeriodicalId":9688,"journal":{"name":"Cellular & Molecular Biology Letters","volume":" ","pages":""},"PeriodicalIF":12.2,"publicationDate":"2026-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13281260/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147590148","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting fibroblast activation protein-α to treat renal fibrosis.","authors":"Li Gong, Xinyu Lu, Na Ma, Tao Lu, Yuhong Gong, Liwei Hao, Weikang Xu, Qianbing Zhang, Xiaolan Chen, Qinglin Mo, Jiexing Tan, Henrique de Paula Lemos, Alexander Speechley, Wenwei Tu, Jianpiao Cai, Lei Huang, Wei Zhu, Sha Wu","doi":"10.1186/s11658-026-00898-9","DOIUrl":"10.1186/s11658-026-00898-9","url":null,"abstract":"<p><p>BACKGROUND: Renal fibrosis is the common outcome of chronic renal disease. Currently, there are no effective therapies. Fibroblast activation and extracellular matrix accumulation are key processes driving renal fibrosis. METHODS AND RESULTS: Fibroblast activation protein (FAP) is highly induced in injured kidneys, and immunofluorescence staining revealed that FAP is mainly expressed in Platelet-derived growth factor receptor-beta (PDGFRβ)+ and alpha-smooth muscle actin (α-SMA)+ myofibroblasts in kidney samples from mice with renal fibrosis and patients with chronic kidney diseases or post-acute kidney injury. In this study, targeting FAP as a strategy for treating renal fibrosis is tested using two preclinical animal models: the mouse models of unilateral ureteral obstruction and unilateral renal ischemia–reperfusion. Adoptive transfer of T cells expressing chimeric antigen receptor specific to FAP or administration of an FAP inhibitor (SP-13786) significantly alleviated kidney fibrosis in both mouse models. Eliminating FAP+ fibroblasts using chimeric antigen receptor T-cell (CAR-T) therapy or inhibiting the FAP prevented fibroblast overactivation, proliferation, and migration, promoted apoptosis, and effectively suppressed other myofibroblast populations. CONCLUSIONS: Overall, we report herein that targeting FAP offers a novel promising treatment approach for renal fibrosis. </p>","PeriodicalId":9688,"journal":{"name":"Cellular & Molecular Biology Letters","volume":" ","pages":""},"PeriodicalIF":12.2,"publicationDate":"2026-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13154437/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147572408","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CDH4/UBA1/RBMX axis promotes polycystic ovary syndrome progression through YAP1 activation.","authors":"Ning Xu, Bo Yu, Yingying Li, Yuxi Yang, Yalong Wang, Lingling Fang, Hongliang Wu, Yingyi Luan, Chenghong Yin","doi":"10.1186/s11658-026-00900-4","DOIUrl":"10.1186/s11658-026-00900-4","url":null,"abstract":"<p><p>BACKGROUND: Polycystic ovary syndrome (PCOS) is the most common endocrine disorder among women of childbearing age. In addition, it is a heterogeneous disease with numerous etiologies, multiple levels, and uneven manifestation. In patients with PCOS, the number of antral follicles is abnormally increased. Several studies indicate and preliminarily support that Hippo pathway abnormalities may contribute to PCOS development by promoting excessive antral follicle proliferation. Moreover, the key Hippo pathway effector, Yes-associated protein 1 (YAP1), contributes to PCOS susceptibility. Furthermore, dysfunction of ovaries in patients with PCOS leads to irregular granulosa cell (GC) growth, which can affect ovulation and cause infertility. Nevertheless, few studies have investigated the key mechanism regulating Hippo activation in PCOS. METHODS: Hippo-associated gene sets and publicly available sequencing databases were used to screen potential PCOS-driving genes, and cadherin 4 (CDH4, R-cadherin) was found to exhibit abnormally high expression in ovarian granulosa cells. Functional studies were conducted to investigate the effects of CDH4 inhibition on PCOS-related ovarian function. RESULTS: A lower CDH4 level ameliorated ovarian function in patients with PCOS by decreasing chronic inflammation and modulating mitochondrial function and apoptosis in GCs. Mechanistically, CDH4 interacts with UBA1 and RBMX, increasing the ubiquitin-dependent degradation of RBMX and finally resulting in the transcriptional activation of YAP1. These results highlight the pivotal role of CDH4 in PCOS, which is achieved through the regulation of the Hippo–YAP1 signaling axis. CONCLUSIONS: This study demonstrates that CDH4 plays a pivotal role in PCOS pathogenesis by regulating the Hippo–YAP1 signaling axis. The finding that reduced CDH4 could enhance the prognosis of individuals with PCOS by regulating ovarian GC activity could potentially inform novel treatment strategies. </p>","PeriodicalId":9688,"journal":{"name":"Cellular & Molecular Biology Letters","volume":" ","pages":""},"PeriodicalIF":12.2,"publicationDate":"2026-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13109888/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147509762","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}