Cellular signalling最新文献

{"title":"EIF2B5 promotes malignant progression of hepatocellular carcinoma by activating the PI3K/AKT signaling pathway through targeting RPL6","authors":"Yiling Xi,&nbsp;Yue Huang,&nbsp;Jiahui Hu,&nbsp;Yan Wang,&nbsp;Qiyi Qian,&nbsp;Linglan Tu,&nbsp;Huizong Nie,&nbsp;Jiayao Zhu,&nbsp;Chenguang Ding,&nbsp;Xiaotao Gao,&nbsp;Xiaoliang Zheng,&nbsp;Dongsheng Huang,&nbsp;Liyan Cheng","doi":"10.1016/j.cellsig.2025.111821","DOIUrl":"10.1016/j.cellsig.2025.111821","url":null,"abstract":"<div><div>Hepatocellular carcinoma (HCC) is a highly aggressive malignancy with limited treatment options and poor prognosis. In this study, we demonstrated the critical role of EIF2B5 in driving HCC progression. We found EIF2B5 expression is significantly upregulated in HCC tumor tissues in several bioinformatics datasets, including The Cancer Genome Atlas, and that high expression of EIF2B5 predicts poor prognosis for HCC patients. Through a series of in vitro cell biology experiments, we found that EIF2B5 knockdown significantly attenuated Hep3B and HepG2 proliferation, migration, and invasion and increased cell cycle arrest, whereas EIF2B5 overexpression promoted HCC progression. Through mass spectrometry and immunoprecipitation validation, we found that EIF2B5 directly interacted with RPL6 and that when EIF2B5 was overexpressed in HCC cells, it promoted the expression of the downstream protein RPL6, which was able to activate the phosphatidylinositol kinase (PI3K)/serine-threonine kinase (AKT)/mammalian target of rapamycin (mTOR) pathway and thereby increase the proliferation and invasion ability of HCC cell lines, as verified by second-generation sequencing analysis and western blot. We further verified these findings using the mouse ectopic tumor assay, and the results showed that EIF2B5 knockdown significantly inhibited tumor progression in HCC mice. The present study suggests that EIF2B5 promotes malignant progression of HCC by interacting with RPL6 and activating the PI3K/AKT/mTOR signaling pathway and may serve as a potential target for the treatment of HCC.</div></div>","PeriodicalId":9902,"journal":{"name":"Cellular signalling","volume":"132 ","pages":"Article 111821"},"PeriodicalIF":4.4,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143848085","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":"Leptin attenuates diabetic cardiomyopathy-induced cardiac remodeling via regulating cGAS/STING signaling and Opa1-mediated mitochondrial fusion","authors":"Xuejiao Zhang ,&nbsp;Chunyuan Hao ,&nbsp;Tonghua Li ,&nbsp;Weihua Gao ,&nbsp;Yang Ren ,&nbsp;Junzhe Wang ,&nbsp;Yuyang Zhang","doi":"10.1016/j.cellsig.2025.111805","DOIUrl":"10.1016/j.cellsig.2025.111805","url":null,"abstract":"<div><h3>Purpose</h3><div>This investigation seeks to elucidate the contribution of leptin to the pathogenesis of diabetic cardiomyopathy (DCM).</div></div><div><h3>Methods</h3><div>Mice were rendered diabetic through the administration of streptozotocin (STZ). Leptin was delivered via subcutaneously implanted osmotic pumps. Assessments of cardiac performance, hypertrophy, and fibrosis were conducted using echocardiography, Hematoxylin and Eosin (H&amp;E), Wheat Germ Agglutinin (WGA), and Masson trichrome staining. Myocardial apoptosis and oxidative stress were quantified through TUNEL assay and biochemical markers of oxidative stress, including Malondialdehyde (MDA), 4-Hydroxynonenal (4-HNE), and 3-Nitrotyrosine (3NT). Mitochondrial structure was examined using Transmission Electron Microscopy (TEM). Primary neonatal cardiomyocytes were subjected to high glucose (HG) conditions. The fluorescent indicators MitoTracker Green and MitoSOX Red were employed to evaluate mitochondrial morphology and function within the cardiomyocytes.</div></div><div><h3>Results</h3><div>Mice with diabetes displayed marked cardiac hypertrophy and fibrosis, as indicated by H&amp;E, WGA, and Masson staining. The administration of leptin significantly mitigated the cardiac pathological manifestations in diabetic mice. Leptin increased the expression of Opa1 and enhanced mitochondrial fusion and function in cardiomyocytes exposed to HG. The cGAS/STING signaling pathway may serve as a pivotal intermediary for leptin to facilitate Opa1-driven mitochondrial fusion.</div></div><div><h3>Conclusions</h3><div>Leptin appears to safeguard against hyperglycemia-induced mitochondrial oxidative damage and DCM by modulating the cGAS/STING signaling cascade and Opa1-mediated mitochondrial fusion. These results propose that leptin could be a promising agent for promoting mitochondrial fusion and preventing diabetes-associated cardiac pathologies.</div></div>","PeriodicalId":9902,"journal":{"name":"Cellular signalling","volume":"132 ","pages":"Article 111805"},"PeriodicalIF":4.4,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143850076","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":"Hedgehog pathway inhibitor HhAntag suppresses virus infection via the GLI-S1PR axis","authors":"Jinyu Zhang ,&nbsp;Chunsheng Dong ,&nbsp;Zhiqiang Chen ,&nbsp;Runbin Hua ,&nbsp;Zhuozheng Li ,&nbsp;Yuzhuo Lin ,&nbsp;Yuqing Wang ,&nbsp;Tingting Feng ,&nbsp;Jianfeng Dai","doi":"10.1016/j.cellsig.2025.111807","DOIUrl":"10.1016/j.cellsig.2025.111807","url":null,"abstract":"<div><div>The interplay between various signaling pathways, including tumor development, immune response, and viral infection, suggests potential mutual regulation within biological systems. To explore this, we screened 85 inhibitors targeting the Notch, Hedgehog, and Wnt signaling pathways to identify the potential antiviral candidates. Using two reporter viruses (VSV-GFP and DENV-Luc), we identified novel inhibitors with antiviral properties. Notably, the Hedgehog pathway inhibitor HhAntag exhibited broad-spectrum antiviral activity, significantly reducing the replication of viruses such as VSV, DENV, ZIKV, and SFTSV. The inhibitory effects of HhAntag were consistent with the downregulation of its target protein, GLI1; while overexpression of GLI1 promoted viral infection. HhAntag did not interfere with viral attachment, entry, or early transcription but specifically inhibited viral protein translation. Additionally, RNA-seq analysis revealed reduced expression of sphingosine-1-phosphate (S1P) signaling pathway receptors, S1PR1 and S1PR5, following HhAntag treatment. HhAntag suppresses virus infection via the GLI-S1PR axis. This study revealed the interplay between tumor-associated Hedgehog (Hh) pathway and viral infection and highlights the potential of HhAntag as a broad-spectrum antiviral drug.</div></div>","PeriodicalId":9902,"journal":{"name":"Cellular signalling","volume":"132 ","pages":"Article 111807"},"PeriodicalIF":4.4,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143839488","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":"The transcription factor BMAL1 inhibits endothelial cell apoptosis by targeting STAT6 to repress its expression","authors":"Qi Yang ,&nbsp;Ya’nan Liang ,&nbsp;Rui Wang ,&nbsp;Tongmei Zhang ,&nbsp;Ruiqing Chai ,&nbsp;Yiquan Yan ,&nbsp;Yateng Tie ,&nbsp;Yongchun Wang ,&nbsp;Xiqing Sun ,&nbsp;Yan Cai ,&nbsp;Xingcheng Zhao","doi":"10.1016/j.cellsig.2025.111812","DOIUrl":"10.1016/j.cellsig.2025.111812","url":null,"abstract":"<div><div>Corneal transparency is critical for optimal visual function, and corneal neovascularization represents the primary cause of visual impairment globally. Recent studies have identified the transcription factor BMAL1 as a significant regulator of angiogenesis. However, its specific role and underlying mechanisms in endothelial cell apoptosis remain inadequately understood. This study seeks to elucidate the role and underlying mechanisms of BMAL1 in endothelial cell apoptosis by employing genetic modification, alkali-burned mouse corneal neovascularization models, lentiviral transfection, proteomic analysis, and other complementary methodologies. Our results showed that BMAL1 expression is significantly elevated in corneal neovascularization induced by alkali burn and removal of <em>Bmal1</em> in endothelial cells resulted in the suppression of corneal neovascularization in alkali burn mouse models. In vivo experiments have demonstrated that the knockout of <em>Bmal1</em> in endothelial cells leads to an increase in endothelial cell apoptosis. Complementary in vitro studies revealed that overexpression of BMAL1 in endothelial cells inhibits apoptosis, while knockdown of BMAL1 promotes apoptosis. Proteomic analysis identified STAT6 as a downstream target of BMAL1 involved in the regulation of endothelial cell apoptosis. Further cell salvage experiments confirmed that BMAL1 modulates endothelial cell apoptosis through the regulation of STAT6 expression. Finally, the results of dual-luciferase reporter assay demonstrated that BMAL1 exerts transcriptional repressive effects on the promoter bound by STAT6. This study elucidates the novel role and mechanism of BMAL1 in the regulation of angiogenesis and endothelial cell apoptosis, thereby identifying a potential therapeutic target for the treatment of vascular diseases such as corneal neovascularization.</div></div>","PeriodicalId":9902,"journal":{"name":"Cellular signalling","volume":"132 ","pages":"Article 111812"},"PeriodicalIF":4.4,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143839489","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":"The super-enhancer regulatory gene SH2D1A promotes the progression of T cell acute lymphoblastic leukemia by activating CHI3L2","authors":"Wanyan Jiao ,&nbsp;Juanjuan Yu ,&nbsp;Zimu Zhang ,&nbsp;Di Wu ,&nbsp;Jian Pan ,&nbsp;Tongjin Yin ,&nbsp;Qijun Yong ,&nbsp;Zong Zhai ,&nbsp;Bi Zhou ,&nbsp;Yumeng Wu ,&nbsp;Yan Li ,&nbsp;Nina Zhou ,&nbsp;Xiaolu Li ,&nbsp;Yanling Chen ,&nbsp;Qian Li ,&nbsp;Tongting Ji ,&nbsp;Tiandan Li ,&nbsp;Qing Zhu ,&nbsp;Ying Yang ,&nbsp;Xin Qi ,&nbsp;Yanfang Tao","doi":"10.1016/j.cellsig.2025.111810","DOIUrl":"10.1016/j.cellsig.2025.111810","url":null,"abstract":"<div><div>T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive leukemia subtype and a prevalent malignancy in children, with poor prognosis, high relapse rates, and drug resistance. Recent research has shown that super-enhancer-regulated genes play crucial roles in T-ALL progression. In this study, we identified SH2 domain containing 1 A (SH2D1A) as a gene regulated by super-enhancers, and is overexpressed, which correlates with unfavorable clinical outcomes in T-ALL. To investigate its role, we silenced SH2D1A expression in T-ALL cell models using RNA interference. This led to a significant reduction in cell proliferation, colony formation, and promoted apoptosis, as demonstrated by CCK-8 assays, soft agar colony formation, and flow cytometry analysis. In vivo, knockdown of SH2D1A significantly inhibited tumor growth and prolonged survival in mice bearing T-ALL. Mechanistically, we found that SH2D1A contributes to T-ALL progression by upregulating CHI3L2, a downstream effector that promotes cell proliferation and inhibits apoptosis. Using ChIP-Seq and RNA-seq technologies, we confirmed that SH2D1A regulates CHI3L2 expression through super-enhancer-mediated regulation in T-ALL cells. Our findings suggest that SH2D1A and CHI3L2 act as oncogenes in T-ALL, and may represent novel therapeutic targets. This research offers new insights into the molecular mechanisms of T-ALL and highlights potential avenues for therapeutic intervention.</div></div>","PeriodicalId":9902,"journal":{"name":"Cellular signalling","volume":"132 ","pages":"Article 111810"},"PeriodicalIF":4.4,"publicationDate":"2025-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143834246","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":"MAD2L1-mediated NANOG nuclear translocation: A critical factor in lung cancer chemoresistance","authors":"Hongye Zhao ,&nbsp;Yongcun Liu ,&nbsp;Longyu Zhu ,&nbsp;Jingge Cheng ,&nbsp;Yishuai Li","doi":"10.1016/j.cellsig.2025.111811","DOIUrl":"10.1016/j.cellsig.2025.111811","url":null,"abstract":"<div><div>This study investigates the function of Mitotic Arrest Deficient 2 Like 1 (MAD2L1) and its role in facilitating NANOG nuclear localization, contributing to chemoresistance in lung cancer. Using both in vivo and in vitro models, we examined MAD2L1 expression in Carboplatin-resistant lung cancer cell lines. The study utilized gene knockdown and overexpression techniques to assess MAD2L1's role in chemoresistance and cell stemness, alongside co-expression analysis and fluorescence staining and CO-IP to explore MAD2L1 and NANOG interactions. Results showed a marked increase in MAD2L1 expression in resistant lung cancer cells, correlating with enhanced cell stemness. MAD2L1 knockdown heightened sensitivity to Carboplatin and reduced NANOG expression, while MAD2L1 overexpression led to increased resistance and stemness. Mechanistically, MAD2L1 facilitated NANOG's nuclear localization, with their co-expression linked to increased cell resistance and metastasis in vivo. These findings suggest that MAD2L1 enhances chemoresistance by promoting NANOG localization, offering insights into potential therapeutic targets for overcoming lung cancer chemoresistance.</div></div>","PeriodicalId":9902,"journal":{"name":"Cellular signalling","volume":"132 ","pages":"Article 111811"},"PeriodicalIF":4.4,"publicationDate":"2025-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143843518","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":"The emerging significance of the METTL family as m6A-modified RNA methyltransferases in head and neck cancer","authors":"Ming Yang ,&nbsp;Zile Zhang ,&nbsp;Hanbin Qin ,&nbsp;Xinhua Lin ,&nbsp;Xuexia Liu ,&nbsp;Hua Zhang","doi":"10.1016/j.cellsig.2025.111798","DOIUrl":"10.1016/j.cellsig.2025.111798","url":null,"abstract":"<div><div>RNA epigenetic modifications are crucial in tumor development, with N6-methyladenosine (m6A) being the most prevalent epigenetic modification found in all eukaryotic messenger RNAs. Accumulating evidence indicates that m6A modifications significantly influence the progression of various malignancies, including head and neck cancer (HNC). The Methyltransferase-like (METTL) family proteins, a group of methyltransferases identified in recent years, function as the “writers” of m6A modifications. These proteins affect RNA stability, translation efficiency, splicing, and localization, thereby regulating diverse cellular functions and promoting tumorigenesis in multiple cancers through their methylation domains. This review aims to summarize existing literature on the METTL family of m6A-modified RNA to elucidate their roles in HNC, providing a theoretical foundation for their potential use as therapeutic targets.</div></div>","PeriodicalId":9902,"journal":{"name":"Cellular signalling","volume":"132 ","pages":"Article 111798"},"PeriodicalIF":4.4,"publicationDate":"2025-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143839464","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":"PSMC2 upregulation enhances epithelial-to-mesenchymal transition in glioblastoma via activating AKT/GSK3β/β-catenin axis","authors":"Pritam Kumar Roy ,&nbsp;K. Deepak ,&nbsp;Prithwish Kola ,&nbsp;Chandan Kanta Das ,&nbsp;Rohit Sesodia ,&nbsp;Sachin A. Borkar ,&nbsp;Mahitosh Mandal","doi":"10.1016/j.cellsig.2025.111809","DOIUrl":"10.1016/j.cellsig.2025.111809","url":null,"abstract":"<div><div>Glioblastoma multiforme (GBM), a grade IV brain tumor, remains one of the most aggressive and difficult-to-treat cancers, emphasizing the urgent need for novel therapeutic targets. The dysregulation of the unfolded protein response, particularly involving the proteasomal pathway, contributes significantly to the pathogenesis of GBM. Proteasome 26S subunit ATPase 2 (PSMC2) has recently been identified as a potential factor in carcinogenesis; however, the molecular mechanisms involved remain unclear. In this study, we found significantly high expression of PSMC2 in GBM, with increased levels associated with an unfavorable prognosis. PSMC2 knockdown in GBM cell lines reduced proliferation, impaired migration, and induced apoptosis, while its overexpression enhanced epithelial-to-mesenchymal transition (EMT) related marker expression. Further, the tumorigenic effect of PSMC2 was confirmed in vivo as PSMC2 knockdown reduced the tumor volume and weight. Mechanistically, PSMC2 promoted malignancy via nuclear localizing of β-catenin by activating AKT/GSK3β/β-catenin axis, with AKT-mediated inhibitory phosphorylation of GSK3β enabling β-catenin activation. Besides, we used Lithium chloride to induce GSK3β phosphorylation which reversed the effects of PSMC2 knockdown, further validating this pathway. These findings demonstrate that PSMC2 drives GBM progression by regulating the AKT/GSK3β/β-catenin axis, positioning it as a promising biomarker and therapeutic target for GBM.</div></div>","PeriodicalId":9902,"journal":{"name":"Cellular signalling","volume":"132 ","pages":"Article 111809"},"PeriodicalIF":4.4,"publicationDate":"2025-04-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143843517","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":"Mechanical stress overload promotes NF-κB/NLRP3-mediated osteoarthritis synovitis and fibrosis through Piezo1","authors":"Likai Yu ,&nbsp;Di Tian ,&nbsp;Zishan Su ,&nbsp;Li Zhang ,&nbsp;Lishi Jie ,&nbsp;Shaobo Guo ,&nbsp;Wenhui Zhu ,&nbsp;Nongshan Zhang ,&nbsp;Peimin Wang","doi":"10.1016/j.cellsig.2025.111786","DOIUrl":"10.1016/j.cellsig.2025.111786","url":null,"abstract":"<div><div>Mechanical stress is a pivotal factor in the development of knee osteoarthritis (KOA). Piezo1, an innovative mechanosensitive ion channel, plays a key role in detecting variations in mechanical stress and transforming them into electrical signals. This research focuses on examining how Piezo1 influences synovial inflammation and fibrosis induced by mechanical stress in KOA, as well as delving into the potential underlying mechanisms. In vivo, pathological changes and immunohistochemical staining were conducted on both normal and overexercise rat synovial tissues to analyze the expression of Piezo1 and the NF-κB/NLRP3 pathways. In vitro utilized a cell stretcher to replicate the mechanical conditions seen in KOA. Levels of pro-inflammatory cytokines and fibrosis-related markers were assessed to investigate the impact of Piezo1 on mechanical stress in fibroblast-like synoviocytes (FLS). Subsequently, following cell stretching interventions, the effects on synovial inflammation and fibrosis were observed with the use of the Piezo1 inhibitor GsMTx4 or the NLRP3 inhibitor MCC950. Mechanical stress significantly promoted the activation of Piezo1, increased the phosphorylation ratio of p65, and elevated the levels of NLRP3, caspase-1, ASC, GSDMD, IL-1β, IL-18, IL-6, and TNF-α. Both in vitro and in vivo, mechanical stress also promoted the occurrence and development of synovial fibrosis, with significant increases in the expression levels of fibrosis-related markers. Under mechanical stress overload, upregulation of Piezo1 can promote the secretion of pro-inflammatory cytokines and the fibrotic process in synovium through the NF-κB/NLRP3 signaling pathway.</div></div>","PeriodicalId":9902,"journal":{"name":"Cellular signalling","volume":"132 ","pages":"Article 111786"},"PeriodicalIF":4.4,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143823467","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":"DDX24 inhibits clear cell renal cell carcinoma progression by directly regulating AKR1B10","authors":"Zhijun Li ,&nbsp;Xinglin Li ,&nbsp;Min Yang ,&nbsp;Xiaofeng Pei ,&nbsp;Taotao Que ,&nbsp;Jianzhong Xian ,&nbsp;Hongjun Jin","doi":"10.1016/j.cellsig.2025.111804","DOIUrl":"10.1016/j.cellsig.2025.111804","url":null,"abstract":"<div><div>Clear cell renal cell carcinoma (ccRCC) is one of the most common malignancies worldwide, but only a few markers have been used to diagnose ccRCC. Here, we report the critical roles of DEAD-box helicase 24 (DDX24), a member of the DEAD-box RNA helicase family, in ccRCC. The DDX24 expression level and its prognostic value were initially detected in public data and then verified in a ccRCC tissue microarray. Subsequent <em>in vitro</em> and <em>in vivo</em> experiments were conducted on representative ccRCC cell lines. RNA sequencing and experimental studies were performed to explore the underlying mechanisms, and the associations between DDX24 expression and immune characteristics were evaluated. DDX24 levels were significantly lower in ccRCC tissues and negatively correlated with advanced clinical stage and overall survival. Functional analyses showed that DDX24 overexpression inhibited ccRCC cell proliferation, migration, and invasion, while DDX24 knockdown enhanced these phenotypes. Mechanistic studies revealed that DDX24 regulated the expression of aldo-keto reductase family 1 member B10 (AKR1B10) and epithelial-mesenchymal transition (EMT)-related transcription factors. Given the low expression of DDX24, ccRCC patients may benefit more from immunotherapies. In conclusion, these findings demonstrate that DDX24 suppresses ccRCC progression through direct regulation of AKR1B10, potentially mediated by EMT-related pathways, which provides potential therapeutic targets for ccRCC.</div></div>","PeriodicalId":9902,"journal":{"name":"Cellular signalling","volume":"132 ","pages":"Article 111804"},"PeriodicalIF":4.4,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143816354","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}