Experimental cell research最新文献

{"title":"Yak FGF12 promotes the proliferation of fibroblasts and longissimus lumborum development","authors":"Nanchi Zhang ,&nbsp;Li Wang ,&nbsp;Yong Wei ,&nbsp;Tianwu An ,&nbsp;Bo Ga ,&nbsp;Lesheng Wang ,&nbsp;Ta E","doi":"10.1016/j.yexcr.2025.114696","DOIUrl":"10.1016/j.yexcr.2025.114696","url":null,"abstract":"<div><div>For a considerable period, fibroblast growth factor 12 (FGF12) was regarded as an intracellularly secreted protein, and with a paucity of research conducted on the effects of FGF12 on cell proliferation. Nevertheless, recent studies have demonstrated that FGF12 can be secreted extracellularly and exhibited bioactive properties. Given the highly conserved motifs characteristic of the FGF family that are present in FGF12, we postulated that it has the potential to stimulate cell proliferation. In this study, we validated the recombinant FGF12 protein's ability to enhance fibroblast proliferation and confer anti-apoptotic properties. The subsequent analyses were conducted using differential gene expression, KEGG pathway, RT-qPCR and Western blotting, which revealed that FGF12 stimulates fibroblast proliferation via the BMP7/Smad signaling pathway. Furthermore, <em>in vivo</em> experimentation with recombinant FGF12 protein revealed its potential to improve growth efficiency, augment blood glucose control and facilitate the development of longissimus lumborum in mice. Collectively, these findings afford novel insights into FGF12's unconventional secretion, its role in regulating cell proliferation, and its promise in promoting muscular development.</div></div>","PeriodicalId":12227,"journal":{"name":"Experimental cell research","volume":"451 1","pages":"Article 114696"},"PeriodicalIF":3.5,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144803899","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":"Chimeric antigen receptor (CAR)-NK cell therapy in gastrointestinal (GI) cancers; a new arena","authors":"Ali G. Alkhathami ,&nbsp;Abdulrahman T. Ahmed ,&nbsp;Ahmed Hussn ,&nbsp;S. RenukaJyothi. ,&nbsp;Rajashree Panigrahi ,&nbsp;Hussein Riyadh Abdul Kareem Al-Hetty ,&nbsp;Hansi Negi ,&nbsp;Pushkar Jassal ,&nbsp;Fathi Jihad Hammady ,&nbsp;Salah Abdulhadi Salih","doi":"10.1016/j.yexcr.2025.114683","DOIUrl":"10.1016/j.yexcr.2025.114683","url":null,"abstract":"<div><div>Tumor microenvironment (TME) is highly complex, and immune escape is a crucial characteristic of malignancies that promotes tumor development and spread. According to studies, the limited success achieved by T cell immunotherapy highlights the growing importance of other advanced immunotherapies, specifically those based on natural killer (NK) cells. Human NK cells are the primary innate immune cells that combat malignancies and exhibit significant diversity within the TME of gastrointestinal (GI) cancers. There is currently a growing interest in the advancement of chimeric antigen receptor (CAR)-engineered NK cells for GI cancer immunotherapy. The advantages of CAR-NK cells over CAR-T cells include enhanced safety, with minimal or no occurrence of cytokine release syndrome (CRS) and graft-versus-host disease (GVHD). Additionally, CAR-NK cells employ many methods to stimulate cytotoxic function and are very feasible for \"off-the-shelf\" manufacture. These effector cells can be genetically altered to specifically recognize different antigens, enhance their ability to multiply and survive in the body, increase their ability to enter GI cancers and overcome resistance in the tumor microenvironment. This ultimately leads to a desired anti-tumor response. Significantly, CAR-NK cells serve as antigen receptors for tumor-associated antigens (TAAs), effectively diverting NK cells and promoting tumor-related immunosurveillance. This study examines the advancements in the therapeutic capabilities of CAR-NK cells for treating GI cancers.</div></div>","PeriodicalId":12227,"journal":{"name":"Experimental cell research","volume":"450 2","pages":"Article 114683"},"PeriodicalIF":3.3,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144682246","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":"Role of METTL3 in high glucose-induced trophoblast cell pyroptosis by the CEBPB/miR-96-5p/CCND2 axis via m6A modification","authors":"Yeqing Su ,&nbsp;Lulu Wang ,&nbsp;Danna He","doi":"10.1016/j.yexcr.2025.114670","DOIUrl":"10.1016/j.yexcr.2025.114670","url":null,"abstract":"<div><div>Gestational diabetes mellitus (GDM) is regarded as abnormally elevated glucose contents at pregnancy period. We attempt to explore the interaction of methyltransferase 3 (METTL3) in high glucose (HG)-treated trophoblast cell pyroptosis, thereby finding a new target for GDM treatment. HTR8/SVneo cells were stimulated using HG to establish GDM models for the following assessment of METTL3, CCAAT enhancer binding protein beta (CEBPB), microRNA (miR)-96-5p and cyclin D2 (CCND2). Levels of pyroptosis-related indicators were verified. m6A level in GDM and the enrichment of m6A on CEBPB were evaluated. The binding relation between CEBPB and miR-96-5p and between miR-96-5p and CCND2 were verified. Roles of METTL3 silencing, CEBPB overexpression, miR-96-5p silencing, and CCND2 overexpression in HG-induced trophoblast cell pyroptosis were detected. METTL3, CEBPB, and CCND2 were upregulated in GDM placenta tissues and HG-induced HTR8/SVneo cells, while miR-96-5p was downregulated. Levels of pyroptosis-related indicators were upregulated, which were counteracted upon METTL3 silencing. Mechanically, METTL3-mediated m6A modification promoted CEBPB expression, inhibited miR-96-5p, which targeted CCND2. CEBPB overexpression, miR-96-5p silencing, and CCND2 could neutralize the suppressive effect of METTL3 knockdown on HG-induced trophoblast cell pyroptosis. METTL3-mediated m6A modification promoted CEBPB expression to suppressmiR-96-5p expression and promote CCND2 expression, thus strengthening HG-induced trophoblast cell pyroptosis.</div></div>","PeriodicalId":12227,"journal":{"name":"Experimental cell research","volume":"450 2","pages":"Article 114670"},"PeriodicalIF":3.5,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144599865","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":"DNAJC6 in acute kidney injury: A novel target for protecting renal tubular epithelial cells through PGC-1α-mediated mitochondrial homeostasis","authors":"Liyun Ma ,&nbsp;Jialiang Hui ,&nbsp;Guangting He ,&nbsp;Zaisheng Qin","doi":"10.1016/j.yexcr.2025.114682","DOIUrl":"10.1016/j.yexcr.2025.114682","url":null,"abstract":"<div><h3>Background</h3><div>Acute kidney injury (AKI) is a severe clinical syndrome that critically threatens patients' lives and health. It is characterized by complex pathogenesis and lacks effective therapeutic strategies. Mitochondrial homeostasis disruption plays a pivotal role in AKI progression, yet its precise molecular mechanisms remain unclear. This study aimed to investigate the role of DNAJC6 in AKI and its molecular mechanism of mitochondrial homeostasis regulation.</div></div><div><h3>Methods</h3><div>Utilizing cisplatin-induced mouse AKI models and human proximal tubular epithelial cell line HK-2, we employed multiple experimental approaches including bioinformatics analysis, cell transfection, immunohistochemical staining, immunofluorescence, TUNEL assay, and mitochondrial function detection to explore the role and molecular mechanisms of DNAJC6 in AKI.</div></div><div><h3>Results</h3><div>In cisplatin-induced AKI models, renal DNAJC6 expression decreased. DNAJC6 overexpression markedly alleviated kidney injury, reduced cell apoptosis, and attenuated inflammatory responses. Mechanistic investigations revealed that DNAJC6 regulated mitochondrial homeostasis by promoting PGC-1α nuclear translocation. Specifically, DNAJC6 improved mitochondrial respiratory function and reduced mitochondrial oxidative stress levels. Moreover, DNAJC6 enhanced mitochondrial biogenesis and suppressed inflammatory factor expression. Upon PGC-1α knockdown, DNAJC6's protective effects were almost completely abolished, confirming that PGC-1α was a critical molecular mediator.</div></div><div><h3>Conclusion</h3><div>This study elucidated the molecular mechanism by which DNAJC6 protected renal tubular epithelial cells through PGC-1α-mediated mitochondrial homeostasis in AKI. These findings not only provide a novel perspective on AKI pathogenesis but also offer a crucial theoretical foundation for developing potential therapeutic strategies. DNAJC6 emerges as a promising molecular target for AKI treatment.</div></div>","PeriodicalId":12227,"journal":{"name":"Experimental cell research","volume":"450 2","pages":"Article 114682"},"PeriodicalIF":3.3,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144697990","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":"Research progress of ASIC family in tumors","authors":"Xing Wan ,&nbsp;Liming Zhou","doi":"10.1016/j.yexcr.2025.114681","DOIUrl":"10.1016/j.yexcr.2025.114681","url":null,"abstract":"<div><div>As a proton-gated cation channel, the acid-sensitive ion channels (ASICs) is capable of sensing changes in the extracellular pH value. ASICs are widely distributed and apart from physiological functions, play a role in various diseases related to acidity, such as pain, inflammation, and ischemia. Moreover, studies have shown that ASICs also have an impact on the occurrence, development, invasion, metastasis, and drug resistance of tumors under acidosis conditions. Although the underlying mechanisms of ASIC-mediated processes have not been extensively explored, these studies suggest that ASICs may emerge as novel biomarkers and therapeutic targets, offering new perspectives for the development of alternative cancer therapies. This article reviews the latest progress of ASICs in tumors, summarizes the classic substances that affect their activity, and analyzes the future research directions, providing a basis for them to be potential targets for tumor treatment.</div></div>","PeriodicalId":12227,"journal":{"name":"Experimental cell research","volume":"450 2","pages":"Article 114681"},"PeriodicalIF":3.3,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144679027","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":"Neutrophil-mediated alteration of CXCL1/IL-8/AR signaling promotes prostate cancer cell proliferation","authors":"Zhifu Liu ,&nbsp;Yuxuan Tian ,&nbsp;Zheng Li ,&nbsp;Zhen Li ,&nbsp;Kehao Yang ,&nbsp;Yiming Zeng ,&nbsp;Jiao Hu ,&nbsp;Yuanwei Li ,&nbsp;Xiongbing Zu ,&nbsp;Shuai Hu","doi":"10.1016/j.yexcr.2025.114680","DOIUrl":"10.1016/j.yexcr.2025.114680","url":null,"abstract":"<div><div>The role of immune cells, particularly neutrophils, in the prostate cancer (PCa) progression remains poorly understood. In this study, we investigated the impact of neutrophils on PCa progression using an in vitro co-culture migration assay. Our findings revealed that PCa cells recruited more neutrophils than normal prostate epithelial cells. Importantly, the recruitment of neutrophils to PCa cells led to increased PCa cell proliferation. Further mechanistic investigations revealed that co-culture of PCa cells with neutrophils led to increased secretion of the chemokine CXCL1. This, in turn, stimulated neutrophils to produce the cytokine IL-8. The enhanced CXCL1/IL-8 signaling axis subsequently amplified androgen receptor (AR) signaling in PCa cells, thereby promoting their proliferation. Disruption of this pathway via IL-8 neutralizing antibodies or AR knockdown reversed the neutrophil-induced PCa cell proliferation. These findings were validated in a mouse model and further supported by clinical sample analysis. Collectively, our study highlights the therapeutic potential of targeting the newly identified signaling cascade involving infiltrating neutrophils within the PCa microenvironment. Understanding and modulating this pathway may offer novel strategies to suppress PCa progression.</div></div>","PeriodicalId":12227,"journal":{"name":"Experimental cell research","volume":"450 2","pages":"Article 114680"},"PeriodicalIF":3.3,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144670436","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":"SIRT7 inhibits osteoclast differentiation in osteoarthritis by mediating NDRG3 deacetylation to suppress the c-Raf/ERK signaling pathway","authors":"Fake Liao ,&nbsp;Yanping Zhang ,&nbsp;Liqin Fu ,&nbsp;Rijiang Chen","doi":"10.1016/j.yexcr.2025.114687","DOIUrl":"10.1016/j.yexcr.2025.114687","url":null,"abstract":"<div><h3>Objective</h3><div>Osteoarthritis (OA) is the most common type of arthritis, mainly triggered by inflammatory factors secreted by chondrocytes and subchondral osteoclasts. SIRT7, an NAD⁺ -dependent deacetylase, is downregulated in OA, but its role in osteoclast differentiation in OA and its underlying molecular regulatory mechanisms remain unclear.</div></div><div><h3>Methods</h3><div>Synovial fluid was collected from 22 patients with osteoarthritis (OA) and 16 healthy individuals. Primary murine bone marrow-derived macrophages (BMMs) were isolated and differentiated into osteoclasts using M-CSF and RANKL. Cell proliferation was assessed using CCK-8 assay. Osteoclast differentiation was evaluated by TRAP staining. Levels of osteoclast differentiation markers (NFATc1, CTSK, and c-FOS) were measured by qRT-PCR. Western blotting was performed to measure the protein level of SIRT7, NDRG3, c-Raf, p-c-Raf, p-ERK, and ERK. Immunoprecipitation (IP) was used to detect acetylation and ubiquitination levels on NDRG3, while co-immunoprecipitation (Co-IP) was employed to examine the interaction between SIRT7 and NDRG3.</div></div><div><h3>Results</h3><div>The expression level of SIRT7 in synovial fluid of OA patients is significantly reduced. Overexpression of SIRT7 markedly inhibits osteoclast differentiation. Additionally, NDRG3 expression is significantly increased in the synovial fluid of OA patients and negatively correlates with SIRT7 expression level. SIRT7 directly binds to NDRG3 protein, reducing its acetylation level and promoting its ubiquitination degradation, thereby inhibiting its expression. Knockdown of NDRG3 suppresses osteoclast differentiation, while overexpression of NDRG3 reverses the effect of SIRT7 on osteoclast differentiation. Furthermore, overexpression of SIRT7 suppresses the levels of p-c-Raf and p-ERK by targeting the downregulation of NDRG3 and thus inhibiting osteoclast differentiation.</div></div><div><h3>Conclusion</h3><div>SIRT7 downregulates NDRG3 expression via directly reducing its acetylation and promoting its ubiquitination degradation, which consequently inhibits the c-Raf/ERK signaling pathway and suppresses osteoclast differentiation in OA. This study provides new insights into the pathophysiology of OA, suggesting that SIRT7 and NDRG3 could be novel molecular markers for the diagnosis and treatment of OA.</div></div>","PeriodicalId":12227,"journal":{"name":"Experimental cell research","volume":"450 2","pages":"Article 114687"},"PeriodicalIF":3.5,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144717830","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":"Comprehensive network pharmacology and experimental study to investigate the effects and mechanisms of Lophatherum gracile Brongn. for glioma treatment","authors":"Zelin Liu ,&nbsp;Lihua Dai ,&nbsp;Qian Jiang ,&nbsp;Simei Zhong ,&nbsp;Jiale Xiong ,&nbsp;Zhe Yang ,&nbsp;Ning Jing ,&nbsp;Yu-Hui Zhang ,&nbsp;Yan Ma","doi":"10.1016/j.yexcr.2025.114671","DOIUrl":"10.1016/j.yexcr.2025.114671","url":null,"abstract":"<div><h3>Background</h3><div>Gliomas are challenging to treat due to their invasive nature and resistance to conventional therapies. Recent study has revealed that <em>Lophatherum gracile Brongn.</em> extract has anti-cancer properties on fibrosarcoma cell. Nevertheless, its medicinal effects and mechanistic pathways on gliomas have not been explored.</div></div><div><h3>Aim of the study</h3><div>To investigate the detailed anti-glioma roles of <em>Lophatherum gracile Brongn.</em> extract and its specific pharmacological routes of action both <em>in vitro</em> and <em>in vivo</em>, focusing on autophagy, apoptosis, proliferation, and migration.</div></div><div><h3>Methods</h3><div>Ethanol extracts of <em>Lophatherum gracile Brongn.</em> were prepared, and the active compounds were appraised by high-performance liquid chromatography. Human glioma cells (A172, LN229, U-87 MG, and U251) were treated with various concentrations of the extract. Immunofluorescence and transmission electron microscopy were employed to investigate the autophagosomes. Cell viability, proliferation, migration, and death were assessed using various assays. The anti-tumor effects were further tested in animal models. Network pharmacology was employed to investigate the potential targets of the main compounds acting on glioma. Furthermore, RNA sequencing was conducted for transcriptome analysis and molecular docking was used for identification.</div></div><div><h3>Results</h3><div>The extract significantly attenuated glioma cell viability, proliferation, and migration, both <em>in vitro</em> and <em>in vivo</em>, while promoting autophagy, apoptosis, and cell death. Five active compounds were identified: chlorogenic acid, isoorientin, orientin, vitexin, and isovitexin. A total of 1472 glioma targets were identified, along with 219 drug targets for the five compounds. Combining analysis of differentially expressed genes revealed that dihydrofolate reductase may be a key target of these compounds, as determined by molecular docking analysis.</div></div><div><h3>Conclusions</h3><div><em>Lophatherum gracile Brongn.</em> extract exhibits significant anti-glioma effects in both cellular and animal models by targeting dihydrofolate reductase, providing novel insights into its therapeutic potential for glioma.</div></div>","PeriodicalId":12227,"journal":{"name":"Experimental cell research","volume":"450 2","pages":"Article 114671"},"PeriodicalIF":3.3,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144616911","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":"Non-canonical role of Yorkie in the development of Malpighian tubules of Drosophila melanogaster","authors":"Priya Singh,&nbsp;Saurabh Chand Sagar,&nbsp;Madhu G. Tapadia","doi":"10.1016/j.yexcr.2025.114679","DOIUrl":"10.1016/j.yexcr.2025.114679","url":null,"abstract":"<div><div>Tissue morphogenesis is a highly coordinated process necessary for correct morphology and function. The Hippo pathway plays a crucial role in regulating the size of organs, and mutation in this pathway can lead to the development of several diseases including tumor. Our study shows that transcriptional coactivator Yorkie, the downstream target of the Hippo pathway, plays a critical role in developing Malpighian tubules in <em>Drosophila</em>. The polycystic phenotype of Malpighian tubules, caused by the loss of the executioner caspase, Drice, results in enhanced expression of Yorkie. Consequently, the genetic reduction of Yorkie in Drice mutants can reduce the polycystic phenotype, reverting it to normal. Yorkie mutation restores actin organization in Drice mutant Malpighian tubules, leading to the proper cellular arrangement. Additionally, improvement in fluid secretion in the Malpighian tubules of Drice mutants was observed when Yorkie levels was reduced. Unexpectedly, Yorkie mutants have greatly elongated Malpighian tubules and its overexpression reduces the size. Collectively, our findings suggest that Yorkie has a non-canonical role in Malpighian tubule development and it genetically interacts with Drice to regulate the development of renal tubule.</div></div>","PeriodicalId":12227,"journal":{"name":"Experimental cell research","volume":"450 2","pages":"Article 114679"},"PeriodicalIF":3.3,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144648964","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":"Hypertension-related genes STOM, MEF2C promote proliferation and migration of clear cell renal cell carcinoma","authors":"Zhixin Huang ,&nbsp;Na Wang ,&nbsp;Yao Dong ,&nbsp;Xiangyu Wang ,&nbsp;Minxin He ,&nbsp;Mingrui Li ,&nbsp;Xiaoshuang Tang ,&nbsp;Delai Fu ,&nbsp;Li Xue ,&nbsp;Tie Chong","doi":"10.1016/j.yexcr.2025.114692","DOIUrl":"10.1016/j.yexcr.2025.114692","url":null,"abstract":"<div><div>As one of the major subtypes of renal cell carcinoma (RCC), there is a distinct paucity of molecular studies exploring the effect of hypertension on the progression of clear cell renal cell carcinoma (ccRCC). In this study, we utilized multi-omics data, integrating it with AddModuleScore and Weighted Gene Co-Expression Network Analysis (WGCNA) algorithms. This approach enabled the identification of 30 hypertension-related genes (HRGs), of which 13 were found to be associated with ccRCC prognosis. The construction of a hypertension-related signature (HRS) utilizing 101 combinations of 10 machine learning algorithms was undertaken, with the objective of demonstrating a noteworthy forecasting capacity for the outcome of patients with ccRCC. In vitro, the co-culture of HUVEC with ccRCC cells has been shown to demonstrate that HUVEC can promote tumor proliferation and migration through the secretion of EGF, FGFB and VEGFA, which is regulated by STOM and MEF2C. Ultimately, through the utilisation of both Mendelian randomization analysis and molecular docking, that Perifosine, 7-Hydroxystaurosporine, and Mitoxantrone could represent efficacious treatment options for ccRCC patients by targeting PRAME. The findings provide novel evidence that hypertension influences the progression of ccRCC and offer new insights into the disease's pathophysiology.</div></div>","PeriodicalId":12227,"journal":{"name":"Experimental cell research","volume":"450 2","pages":"Article 114692"},"PeriodicalIF":3.5,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144750740","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}