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Expression profiles and prognostic relevance of mitochondrial-related gene sets were analyzed using TCGA data, identifying SLC25A3 as significantly overexpressed with poor outcomes. Additional clinical sample analyses and in vivo/in vitro experiments tested functional roles. Multi-omics sequencing further explored causality, showing oncogenic effects may be mediated via regulation of mitochondrial function and chromatin remodeling.",{"@graph":69,"@context":122},[70,84,105],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":35,"@type":76,"position":81},"https://docshare.wps.com/document/healthcare/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/slc25a3-promotes-hepatocellular-carcinoma-progression-by-inducing-mitochondrial-dysfunction-and-chromatin-remodeling/448523/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/slc25a3-promotes-hepatocellular-carcinoma-progression-by-inducing-mitochondrial-dysfunction-and-chromatin-remodeling/448523.png","ImageObject",300,407,{"name":92,"@type":93},"\tJames","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-22","2026-09-30",true,{"@type":102,"interactionType":103,"userInteractionCount":81},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"What was the main goal of this study on SLC25A3 in HCC?","Question",{"text":112,"@type":113},"To elucidate the role and mechanism of SLC25A3 in hepatocellular carcinoma.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"How did the study evaluate SLC25A3 expression and prognosis?",{"text":117,"@type":113},"It analyzed mitochondrial-related gene expression profiles and prognostic implications in HCC using TCGA data, then confirmed findings using clinical samples and functional experiments.",{"name":119,"@type":110,"acceptedAnswer":120},"What mechanisms were proposed to explain how SLC25A3 promotes HCC?",{"text":121,"@type":113},"The oncogenic effects were suggested to be mediated through regulation of mitochondrial function and chromatin remodeling.","https://schema.org",{"og:url":83,"og:type":124,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":126,"canonical":83},"index,follow",{"doc_id":128,"site_id":62},448523,1791768876,{"code":4,"msg":5,"data":131},{"doc_id":128,"user_id":132,"nickname":92,"user_avatar":133,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":81,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":139,"language":140,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":141,"faqs":142,"seo_title":143,"seo_description":67,"update_tm":144,"read_time":41,"preview_page_count":4},2336474466412,"https://ap-avatar.wpscdn.com/davatar_155a257f0dc6eb9ab79c44ca47cae57d","SLC25A3 promotes hepatocellular carcinoma progression by inducing mitochondrial dysfunction and chromatin remodeling  \nShuangya Deng1,2, Jie Fu2  \n1Department of General Surgery, Guilin Hospital of the Second Xiangya Hospital, Central South University, Guilin, China; 2Department of General Surgery, The Second Xiangya Hospital, Central South University, Changsha, China  \nContributions: (I) Conception and design: J Fu; (II) Administrative support: J Fu; (III) Provision of study materials or patients: Both authors; (IV) Collection and assembly of data: S Deng; (V) Data analysis and interpretation: Both authors; (VI) Manuscript writing: Both authors; (VII) Final  \napproval of manuscript: Both authors.  \nCorrespondence to: Jie Fu, MD, PhD. Department of General Surgery, The Second Xiangya Hospital, Central South University, No. 139 Renmin  \nRoad, Changsha 410011, China. Email: [fujie2016@csu.edu.cn](fujie2016@csu.edu.cn).  \nBackground: Hepatocellular carcinoma (HCC) represents one of the most life-threatening malignancies globally. Despite significant advancements in the treatment of HCC in recent years, therapeutic outcomes remain unsatisfactory, particularly for patients with advanced, inoperable HCC. Thus, there is an urgent need to identify novel therapeutic targets and develop combination therapies to enhance treatment efficacy.  \nThe aim of this study is to elucidate the role and mechanism of solute carrier family 25 member A3 (SLC25A3)  \nin HCC.  \nMethods: In this study, we examined the expression profiles and prognostic implications of mitochondrialrelated gene sets in HCC using data from The Cancer Genome Atlas (TCGA) database. Among these genes, SLC25A3, a mitochondrial membrane protein, was found to be significantly overexpressed in HCC and associated with poor prognosis. To explore the potential role of SLC25A3 in HCC, we conducted analyses of clinical samples and performed in vivo and in vitro experiments. The underlying mechanisms were further  \ninvestigated using multi-omics sequencing techniques.  \nResults: The experimental results confirmed that SLC25A3 plays an on co genic role in hepatocarcinogenesis, potentially by inducing mitochondrial dysfunction. Further multi-omics analysis revealed that the oncogenic effects of SLC25A3 in HCC may be mediated through its regulation of  \nmitochondrial function and chromatin remodeling.  \nConclusions: These findings offer valuable insights for identifying potential therapeutic targets for HCC.  \nKeywords: SLC25A3; hepatocellular carcinoma (HCC); mitochondrial; metabolism; chromatin remodeling  \nSubmitted Sep 04, 2025. Accepted for publication Oct 30, 2025. Published online Dec 29, 2025.  \ndoi: 10.21037/tcr-2025-1946  \nView this article at: [https://dx.doi.org/10.21037/tcr-2025-1946](https://dx.doi.org/10.21037/tcr-2025-1946)  \nIntroduction  \nLiver cancer is one of the most prevalent malignancies of the digestive system worldwide, with more than 900,000 new cases annually, accounting for 4.7% of all newly diagnosed cancers globally, ranking sixth. Despite these numbers, liver cancer causes over 800,000 deaths each year, representing 8.3% of cancer-related fatalities, second only to lung cancer (1) . Hepatocellular carcinoma (HCC), the most common subtype of liver cancer, accounts for over  \n90% of cases. In recent years, advancements in surgical techniques, along with improvements in diagnostic and therapeutic approaches, have significantly improved the overall prognosis of HCC patients (2,3). However, for those with advanced, inoperable HCC, current treatment options remain limited, and prognosis remains poor. Therefore, there is an urgent need to identify novel therapeutic targetsand develop synergistic treatment strategies to enhance therapeutic efficacy, improve patients’ quality of life, and  \n© AME Publishing Company. Transl Cancer Res 2025;14(12):8301-8312 | [https://dx.doi.org/10.21037/tcr-2025-1946](https://dx.doi.org/10.21037/tcr-2025-1946)  \n8302 Deng and Fu. SLC25A","cbCaimtEVmfpeif6","https://ap.wps.com/l/cbCaimtEVmfpeif6","pdf",7848303,12,"English","# Background\n# Aim\n# Methods\n# Results\n# Conclusions\n# Keywords\n# Introduction\n# Key findings","[{\"question\":\"What was the main goal of this study on SLC25A3 in HCC?\",\"answer\":\"To elucidate the role and mechanism of SLC25A3 in hepatocellular carcinoma.\"},{\"question\":\"How did the study evaluate SLC25A3 expression and prognosis?\",\"answer\":\"It analyzed mitochondrial-related gene expression profiles and prognostic implications in HCC using TCGA data, then confirmed findings using clinical samples and functional experiments.\"},{\"question\":\"What mechanisms were proposed to explain how SLC25A3 promotes HCC?\",\"answer\":\"The oncogenic effects were suggested to be mediated through regulation of mitochondrial function and chromatin remodeling.\"}]","SLC25A3 promotes hepatocellular carcinoma progression by inducing mitochondrial dysfunction and chromatin remodeling | PDF",1790727582]