Experimental cell research最新文献

{"title":"TGF-β-induced acetylation of KLF5 drives TNFAIP2 transcription and EMT in nasopharyngeal carcinoma: Unveiling a novel regulatory mechanism","authors":"Yi Qian ,&nbsp;Xuxu Zhao ,&nbsp;Feiyang Wu ,&nbsp;Xiaoqiang Wang ,&nbsp;Tao Chen","doi":"10.1016/j.yexcr.2025.114498","DOIUrl":"10.1016/j.yexcr.2025.114498","url":null,"abstract":"<div><div>Epithelial-mesenchymal transition (EMT) is one of the critical mechanisms underlying migration, invasion, and metastasis of nasopharyngeal carcinoma (NPC) cells. The transcription factor KLF5 plays a pivotal role in various cancers, however, its precise functions in NPC remain incompletely understood. This study aims to explore the detailed mechanisms by which TGF-β enhances TNFAIP2 transcription by acetylating KLF5, thereby inducing EMT in NPC. KLF5 was significantly overexpressed in NPC tissues and closely associated with adverse clinicopathological features of the patients. Further studies revealed that TGF-β markedly increased the expression of KLF5 and its acetylated form, Ac-KLF5, in NPC cells, with the acetylation status of KLF5 being crucial for its function. KLF5 induced EMT in NPC cells by directly binding to the TNFAIP2 promoter and promoting its transcription. The pro-migratory and pro-invasive effects of acetylated KLF5 on NPC cells depended on TNFAIP2. Additionally, in vivo experiments confirmed that TGF-β treatment induced tumors in NPC mouse models to exhibit apparent EMT characteristics. These results collectively support the central role of the TGF-β-KLF5-TNFAIP2 axis in EMT of NPC. This study elucidates the specific mechanisms by which TGF-β promotes TNFAIP2 transcription by acetylating KLF5, thereby inducing EMT in NPC. This discovery not only provides new insights into the pathogenesis of NPC but also identifies potential therapeutic targets for NPC treatment.</div></div>","PeriodicalId":12227,"journal":{"name":"Experimental cell research","volume":"447 1","pages":"Article 114498"},"PeriodicalIF":3.3,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143578626","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ano5 deficiency disturbed bone formation by inducing osteoclast apoptosis in Gnathodiaphyseal dysplasia","authors":"Xiu Liu ,&nbsp;Shengnan Wang ,&nbsp;Chao Liang ,&nbsp;Shuai Zhang ,&nbsp;Sirui Liu ,&nbsp;Ying Hu","doi":"10.1016/j.yexcr.2025.114493","DOIUrl":"10.1016/j.yexcr.2025.114493","url":null,"abstract":"<div><div>Gnathodiaphyseal dysplasia (GDD) is a rare genetic syndrome characterized by cemento-ossifying fibroma lesions in the mandible and sclerosis of tubular bones. Currently, the clinical treatment of GDD is limited to surgical resection; therefore, novel treatment strategies developed through exploration of the related mechanisms are needed. Mutations in the TMEM16E/ANO5 gene are considered the main pathogenic factor of GDD, and the <em>Ano5</em> knockout mouse model (<em>Ano5</em>^{<em>−/−</em>}) established previously, which presented GDD-like characteristics, exhibited decreased osteoclastogenesis. <em>ANO5</em>, a calcium-activated chloride channel (CaCC), plays an important role in the maintenance of intracellular calcium homeostasis, which is crucial for osteoclast differentiation. In this study, our data indicated that the intracellular calcium concentration ([Ca²⁺]_i) and calcium transients were significantly decreased in <em>Ano5</em>^{<em>−/−</em>} osteoclasts accompanied by abnormally altered expression of calcium transporters, resulting in calcium dyshomeostasis. In addition, the endoplasmic reticulum stress (ERS) response was significantly enhanced in <em>Ano5</em>^{<em>−/−</em>} osteoclasts, possibly because of calcium dyshomeostasis, which leading to the increased proportion of apoptotic osteoclasts via the activation of the C/EBP homologous protein (CHOP) signalling pathway, accompanied by abnormal changes in the expression of apoptosis-related factors. In summary, <em>Ano5</em> deficiency impairs the function of osteoclasts by increasing osteoclast apoptosis, which is induced by an overactivated ERS response via calcium dyshomeostasis.</div></div>","PeriodicalId":12227,"journal":{"name":"Experimental cell research","volume":"447 1","pages":"Article 114493"},"PeriodicalIF":3.3,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143550256","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Protocadherin 17 weakens the lenvatinib resistance of liver cancer through inducing ferroptosis","authors":"Jun Yang ,&nbsp;Bin Hu ,&nbsp;Guowei Zhang ,&nbsp;Kai Wu ,&nbsp;Xue Zhang ,&nbsp;Mengxuan Ji ,&nbsp;Bin Zhang ,&nbsp;Hengliang Shi ,&nbsp;Dechun Li","doi":"10.1016/j.yexcr.2025.114495","DOIUrl":"10.1016/j.yexcr.2025.114495","url":null,"abstract":"<div><div>Lenvatinib has been employed in the treatment of advanced liver cancer; however, its clinical application is significantly impeded by frequent drug resistance. Recent studies have revealed that lenvatinib treatment triggers ferroptosis in liver cancer cells, providing a novel approach to addressing lenvatinib resistance. In this study, we initially validated the induction of ferroptosis by lenvatinib in liver cancer cells. Remarkably, protocadherin 17 (PCDH17), an adhesion-related protein, was found to be down-regulated in liver cancer, and overexpression of PCDH17 could induce ferroptosis in liver cancer cells. Importantly, silencing PCDH17 inhibited the impact of lenvatinib on liver cancer cell ferroptosis, while overexpression of PCDH17 had the opposite effect. These findings were further confirmed using a xenograft tumor model in BALB/c nude mice. Additionally, lenvatinib-resistant (LR) liver cancer cells were generated for additional validation purposes. It was observed that LR-liver cancer cells lost their susceptibility to ferroptosis induction by lenvatinib; however, overexpression of PCDH17 reactivated their sensitivity to ferroptosis. Corresponding results were also verified in BALB/c nude mice models. In conclusion, these results suggest that as a novel regulator of ferroptosis, PCDH17 can alleviate lenvatinib resistance and potentially enhance the therapeutic efficacy of lenvatinib in treating liver cancer.</div></div>","PeriodicalId":12227,"journal":{"name":"Experimental cell research","volume":"447 1","pages":"Article 114495"},"PeriodicalIF":3.3,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143561765","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Btbd8 deficiency exacerbates bleomycin-induced pulmonary fibrosis in mice by enhancing myofibroblast accumulation and inflammatory responses","authors":"Xiaoqiong Yang ,&nbsp;Qiman Dong ,&nbsp;Xingyuan Tong ,&nbsp;Xiaoling Du ,&nbsp;Lingyi Chen","doi":"10.1016/j.yexcr.2025.114494","DOIUrl":"10.1016/j.yexcr.2025.114494","url":null,"abstract":"<div><div>BTBD8 contributes to the pathogenesis of inflammatory bowel disease through regulating intestinal barrier integrity and inflammation. However, its role in idiopathic pulmonary fibrosis (IPF) remains unknown. Here we investigated whether BTBD8 plays a role in bleomycin-induced pulmonary fibrosis. Pulmonary fibrosis was induced in wild-type (WT) and <em>Btbd8</em> knockout (KO) mice by intratracheal instillation of bleomycin. The mice were sacrificed on day 7 or 12. Subsequently, the progression of bleomycin-induced pulmonary fibrosis was assessed. We found that <em>Btbd8</em> KO mice are more susceptible to bleomycin-induced pulmonary fibrosis, with more severe body weight loss and pulmonary injury, increased collagen deposition and myofibroblast accumulation. We further demonstrated that BTBD8 functions in pulmonary fibroblasts to suppress the conversion of fibroblasts to myofibroblasts. Moreover, <em>Btbd8</em> deficiency promotes the infiltration of inflammatory cells and the secretion of pro-inflammatory cytokines in IPF mouse model. These results highlight the critical role of BTBD8 in the pathogenesis of bleomycin-induced pulmonary fibrosis in mice, and suggest that BTBD8 may alleviate bleomycin-induced fibrosis by suppressing the differentiation of fibroblasts to myofibroblast, as well as inflammatory responses.</div></div>","PeriodicalId":12227,"journal":{"name":"Experimental cell research","volume":"447 1","pages":"Article 114494"},"PeriodicalIF":3.3,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143572562","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Low extracellular pH enhances TRAIL-induced apoptosis by downregulating Mcl-1 expression","authors":"Farzaneh Vafaeinik ,&nbsp;Lin Zhang ,&nbsp;Yong J. Lee","doi":"10.1016/j.yexcr.2025.114481","DOIUrl":"10.1016/j.yexcr.2025.114481","url":null,"abstract":"<div><div>We previously reported that low extracellular pH promotes tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced apoptosis through the mitochondria-mediated caspase signal transduction pathway. In this study, we further investigated the mechanism of low extracellular pH on TRAIL-induced apoptosis. When human colorectal carcinoma HCT116 cells were treated with TRAIL for 4 h, significant cytotoxicity was observed at pH 6.3, while cytotoxic effects were notably reduced at pH 7.2. These findings suggest that TRAIL's cytotoxic effects on human colorectal cancer cells are enhanced in low pH environments following TRAIL treatment. Similar results were observed in human pancreatic adenocarcinoma BxPC-3 cells. Interestingly, TRAIL was found to downregulate the levels of anti-apoptotic proteins, such as Mcl-1. This was confirmed by the knock-in (KI) of an Mcl-1 phosphorylation site mutant in HCT116 cells, which blocked TRAIL-induced Mcl-1 downregulation and the subsequent apoptotic response. These results indicate that Mcl-1 mediates TRAIL resistance in the Mcl-1 KI cells. Additionally, our results revealed that TRAIL significantly induced JNK phosphorylation in HCT116 cells, suggesting the involvement of JNK in TRAIL-induced cell death in colorectal cancer cells. Our findings demonstrate that low extracellular pH enhances TRAIL-induced cytotoxicity, particularly at pH 6.3 and 6.6. Moreover, the anti-apoptotic Bcl-2 family member Mcl-1 is an important target of TRAIL in colorectal carcinoma HCT116 cells under different low pH conditions. TRAIL triggered a rapid decline in Mcl-1, suggesting that Mcl-1 downregulation is crucial for TRAIL-induced apoptosis.</div></div>","PeriodicalId":12227,"journal":{"name":"Experimental cell research","volume":"447 1","pages":"Article 114481"},"PeriodicalIF":3.3,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143537029","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Glycolysis-related gene signatures and the functional role of P4HA1 in osteosarcoma prognosis","authors":"Haoran Gui ,&nbsp;Shuai Wang ,&nbsp;Bo Li","doi":"10.1016/j.yexcr.2025.114492","DOIUrl":"10.1016/j.yexcr.2025.114492","url":null,"abstract":"<div><div>Osteosarcoma, a primary malignant bone tumor predominantly affecting children and adolescents, is characterized by aerobic glycolysis, which is intricately linked to tumor progression and metastasis, yet its prognostic implications remain underexplored. This study aimed to develop a prognostic model utilizing glycolysis-related genes and to elucidate the functional role of P4HA1, a key gene within this model, in osteosarcoma prognosis and immune cell infiltration. We collected clinical and transcriptomic data from osteosarcoma patients in the UCSC Xena and GEO databases. Through univariate Cox and LASSO regression analyses, we identified 12 glycolysis-related genes that significantly influence osteosarcoma prognosis. These genes were employed to construct a risk score model, which accurately predicted patient outcomes as demonstrated by survival analysis and ROC curves, with an AUC of 0.899, 0.881, and 0.878 for 1-year, 3-year, and 5-year survival predictions, respectively. The model was particularly effective across different clinical subgroups. Immune cell infiltration analysis revealed that CD8⁺ T cells, naïve CD4⁺ T cells, resting dendritic cells, and activated mast cells significantly contributed to the model's predictive power. The model also showed significant enrichment of immune-related signaling pathways, indicating a robust association between immune status and glycolytic-related risk scores in osteosarcoma prognosis. Notably, P4HA1 was upregulated in osteosarcoma tissues and promoted cell proliferation in a glycolysis-dependent manner, as evidenced by increased intracellular ATP levels, inhibited glucose absorption, and elevated lactate levels in P4HA1-overexpressing osteosarcoma cells. The promotion of proliferation by P4HA1 could be significantly attenuated by the glycolysis inhibitor 2-DG, highlighting the glycolysis dependency of P4HA1's action. In conclusion, we developed a prognostic model for osteosarcoma by integrating glycolysis-related genes, with a particular emphasis on the functional role of P4HA1. Our findings highlight the interplay between glycolysis and immune cell infiltration in disease prognosis. This model provides insights for targeted therapies and a foundation for further research into osteosarcoma treatment.</div></div>","PeriodicalId":12227,"journal":{"name":"Experimental cell research","volume":"447 1","pages":"Article 114492"},"PeriodicalIF":3.3,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143537027","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ELAVL1 facilitates gastric cancer progression and metastasis through TL1A mRNA stabilization","authors":"Tao Jiang ,&nbsp;Sihan Bo ,&nbsp;Yong You ,&nbsp;Yongwei Wang ,&nbsp;Lei Hou ,&nbsp;Shuang Tian ,&nbsp;Bing Bai ,&nbsp;Yu Cheng ,&nbsp;Yaxian Gao","doi":"10.1016/j.yexcr.2025.114491","DOIUrl":"10.1016/j.yexcr.2025.114491","url":null,"abstract":"<div><div>ELAV-like RNA-binding protein 1 (ELAVL1) is a key RNA-binding protein involved in tumor progression and metastasis. This study identifies a previously unrecognized interaction between ELAVL1 and <em>TL1A</em> mRNA, elucidating its role in promoting gastric cancer (GC) progression through the activation of the PI3K/Akt signaling pathway. Overexpression of ELAVL1 significantly enhances the proliferation and migration of GC cells, whereas silencing ELAVL1 leads to a marked reduction in these processes. Additionally, stable knockout of ELAVL1 significantly inhibits the growth of xenograft tumors derived from GC cells in nude mice. Mechanistically, ELAVL1 directly binds to <em>TL1A</em> mRNA through its RNA recognition motifs (RRM1 and RRM3). The binding sites on <em>TL1A</em> mRNA have been confirmed in two regions: one located between nucleotides 1605 and 1868, and the other between 4324 and 4587. ELAVL1 stabilizes <em>TL1A</em> mRNA expression and promotes GC progression by activating the downstream PI3K/Akt signaling pathway.Our findings highlight a novel regulatory axis involving ELAVL1, <em>TL1A</em> mRNA, and PI3K/Akt, providing new insights into RNA-mediated oncogenic signaling and establishing ELAVL1 as a potential therapeutic target for GC. This discovery lays the groundwork for developing targeted therapies against ELAVL1.</div></div>","PeriodicalId":12227,"journal":{"name":"Experimental cell research","volume":"446 2","pages":"Article 114491"},"PeriodicalIF":3.3,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143529288","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Deciphering the role of circulating miRNAs in the etiology and pathophysiology of endometriosis: An updated compiled review","authors":"Anuja Pant ,&nbsp;Kareena Moar ,&nbsp;Taruna K. Arora ,&nbsp;Tikam Chand Dakal ,&nbsp;Vipin Ranga ,&nbsp;Narendra Kumar Sharma ,&nbsp;Pawan Kumar Maurya","doi":"10.1016/j.yexcr.2025.114482","DOIUrl":"10.1016/j.yexcr.2025.114482","url":null,"abstract":"<div><div>Endometriosis is characterized by the presence of endometrial tissue outside of the uterus. It is a benign chronic condition with incapacitating symptoms like infertility and pelvic pain. Endometriosis has a detrimental impact on the reproductive health of women, placing a heavy financial strain on the medical system. It is a multifactorial disorder governed by numerous mechanisms or risk factors that contribute to the pathologies of the disease. With limitations in diagnostics techniques, it is challenging to detect the disease at an initial stage. In around 1 % of endometriotic patients malignant state may reach, leading to severe consequences. To overcome such challenges, at present, numerous circulating miRNAs have been studied in plasma or serum samples from patients with endometriosis to develop a non-invasive diagnostic biomarker-based tool to identify the disease early. Our review compiles the miRNAs in bodily fluids that are linked with endometriosis-related mechanisms, which may serve as a potential biomarker. Some of these mechanisms are common in both cancer and endometriosis. Additionally, we have also emphasised the miRNAs with a putative role in cancer development and progression that could be used as a biomarker. This may further aid in protecting the 1 % of affected females from ovarian, breast, and in some cases endometrial cancer. We have come across several miRNAs associated with multiple mechanisms associated with endometriosis. miR-199a and miRNAs-let-7 family are some of the most common miRNAs that assist in multiple mechanisms such as cell proliferation, invasion, apoptosis, and epithelial-mesenchymal transition. Strategic planning and additional investigation into the identified miRNAs would make them a viable therapeutic target for the optimal management of endometriosis.</div></div>","PeriodicalId":12227,"journal":{"name":"Experimental cell research","volume":"446 2","pages":"Article 114482"},"PeriodicalIF":3.3,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143519219","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Silencing of LOX-1 attenuates high glucose-induced ferroptosis in THVECs via the HIF-1α/SLC7A11 signaling pathway","authors":"Haiqi Zhang ,&nbsp;Xinying Chang ,&nbsp;Xuan Liu ,&nbsp;Baozhuan Zhang ,&nbsp;Rongrong Wang ,&nbsp;Yuhui Wang ,&nbsp;Simeng Dai ,&nbsp;Tonghan Yao ,&nbsp;Qi Zhang","doi":"10.1016/j.yexcr.2025.114451","DOIUrl":"10.1016/j.yexcr.2025.114451","url":null,"abstract":"<div><h3>Objectives</h3><div>Diabetic osteoporosis (DOP) represents a significant and serious complication associated with diabetes, characterized by a complex and inadequately understood pathophysiological mechanism. Recent studies have highlighted a robust association between DOP and ferroptosis. H-type vessels play a critical role in osteoporosis, while lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) is associated with endothelial dysfunction related to diabetes. In this study, we investigate how LOX-1 affects ferroptosis in H-type vascular endothelial cells (THVECs) under high glucose (HG) conditions, aiming to elucidate the molecular mechanisms involved.</div></div><div><h3>Methods</h3><div>THVECs were isolated from rats employing an enzymatic digestion method and subsequently validated through immunofluorescence analysis. The silencing of LOX-1 was achieved via transfection with a lentiviral vector. Cell viability was assessed using the CCK-8 assay, and ROS, MMP, GSH, MDA, and Fe²⁺ levels were assessed utilizing specific commercial kits. Western blotting and PCR assessed LOX-1, HIF-1α, SLC7A11, and GPX4 expression levels.</div></div><div><h3>Results</h3><div>In high glucose conditions, LOX-1 expression at both protein and mRNA levels increased, while ROS, MDA, and Fe²⁺ rose, and MMP and GSH levels fell, resulting in ferroptosis in THVECs. This condition could be reversed by silencing LOX-1 or by administering the ferroptosis inhibitor (Fer-1). Further analysis showed that silencing LOX-1 enhanced the expression of HIF-1α, SLC7A11, and GPX4, which mitigated ferroptosis in THVECs.</div></div><div><h3>Conclusions</h3><div>Downregulation of LOX-1 alleviates high glucose-induced ferroptosis in THVECs via the HIF-1α/SLC7A11 pathway. This suggests that LOX-1 functions as a critical target for regulating ferroptosis in THVECs, providing a novel insight into the pathological mechanisms associated with DOP.</div></div>","PeriodicalId":12227,"journal":{"name":"Experimental cell research","volume":"446 2","pages":"Article 114451"},"PeriodicalIF":3.3,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143522970","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A m6A writer RBM15 enhances the cell malignancy of osteosarcoma by mediating m6A modification of lncRNA THAP9-AS1","authors":"Hao Zou ,&nbsp;Fei Hu ,&nbsp;Xin Wu ,&nbsp;Bin Xu ,&nbsp;Guifeng Shang ,&nbsp;Dong An ,&nbsp;Dehao Qin ,&nbsp;Xiaolei Zhang ,&nbsp;Aofei Yang","doi":"10.1016/j.yexcr.2025.114490","DOIUrl":"10.1016/j.yexcr.2025.114490","url":null,"abstract":"<div><h3>Background</h3><div>Osteosarcoma (OS) remains a potentially fatal disease in children. Increasing evidence highlights the implication of lncRNAs and N6-methyladenosine (m6A) modification in OS malignancies. Here, we aimed to decipher the pathological significance of RBM15-mediated m6A modification of lncRNA THAP9-AS1 in OS progression.</div></div><div><h3>Methods</h3><div>The expression levels of THAP9-AS1 and RBM15 in OS tissues and cell lines was determined by qRT-PCR. Based on the abnormal regulation of THAP9-AS1 and RBM15, the CCK8, colony-formation, and transwell invasion assays were used to evaluate the viability, clone formation capacity, and invasive ability of OS cells. A mouse model of tumor transplantation was utilized to ascertain the role of THAP9-AS1 silencing <em>in vivo</em>. The relationship between THAP9-AS1 and RBM15 was determined by RIP and MeRIP assays.</div></div><div><h3>Results</h3><div>THAP9-AS1 and RBM15 were significantly elevated in OS. Silencing of THAP9-AS1 or RBM15 decreased the proliferative and invasive ability of OS cells <em>in vitro</em>, and inhibition of THAP9-AS1 delayed the tumorous growth <em>in vivo</em>. Interestingly, THAP9-AS1 binds to RBM15, and was stimulated by RBM15 to promote m6A level and translation. Furthermore, THAP9-AS1 upregulation promoted OS cell invasion and survival, and this promotion of OS cell malignancy was abrogated by RBM15 silencing.</div></div><div><h3>Conclusion</h3><div>THAP9-AS1 serves as a tumor promoter by accelerating the malignant progression of OS by undergoing m6A modification, which is mediated by RBM15. This suggests that RBM15-m6A-THAP9-AS1 may be a potential target for OS treatment.</div></div>","PeriodicalId":12227,"journal":{"name":"Experimental cell research","volume":"447 1","pages":"Article 114490"},"PeriodicalIF":3.3,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143522968","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}