{"title":"ACOXL-AS1's pan-cancer dynamics and its proliferative impact on endometrial endometrioid carcinoma.","authors":"Hongrong Wu, Ruilin Lin, Liangli Hong","doi":"10.1186/s12885-025-15005-y","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Long non-coding RNAs (lncRNAs) are critically involved in carcinogenesis; however, the pan-cancer significance and functional mechanisms of ACOXL-AS1 remain largely uncharacterized. This study comprehensively investigates the expression landscape, prognostic value, and biological impact of ACOXL-AS1 across multiple malignancies, with a specific focus on its pro-proliferative role in endometrial endometrioid carcinoma (EEC).</p><p><strong>Methods: </strong>We analyzed ACOXL-AS1 expression and its association with clinical outcomes using pan-cancer RNA-seq data from TCGA and GTEx databases. Functional validation was performed in EEC cell lines (HHUA, HEC-1 A) via lentivirus-mediated overexpression, followed by CCK-8, colony formation, and transwell migration/invasion assays. Mechanistic insights were investigated using integrated bioinformatics approaches.</p><p><strong>Results: </strong>ACOXL-AS1 was significantly downregulated in most cancers, and higher expression correlated with improved prognosis. Elevated ACOXL-AS1 levels were associated with smaller tumor size, lower disease stage, reduced metastasis, and decreased tumor mutational burden (TMB)/microsatellite instability (MSI). It also modulated the immunosuppressive tumor microenvironment. Critically, ACOXL-AS1 overexpression significantly inhibited EEC cell proliferation, migration, invasion, and tumor growth in xenograft models. Mechanistically, it may regulate RPA4 expression through the homologous recombination pathway in EEC cells.</p><p><strong>Conclusions: </strong>ACOXL-AS1 may play a role as a tumor suppressor in endometrial endometrioid carcinoma (EEC), suggesting its potential as a prognostic biomarker and a candidate for further exploration as a therapeutic target.</p>","PeriodicalId":9131,"journal":{"name":"BMC Cancer","volume":"25 1","pages":"1522"},"PeriodicalIF":3.4000,"publicationDate":"2025-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"BMC Cancer","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1186/s12885-025-15005-y","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"ONCOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Background: Long non-coding RNAs (lncRNAs) are critically involved in carcinogenesis; however, the pan-cancer significance and functional mechanisms of ACOXL-AS1 remain largely uncharacterized. This study comprehensively investigates the expression landscape, prognostic value, and biological impact of ACOXL-AS1 across multiple malignancies, with a specific focus on its pro-proliferative role in endometrial endometrioid carcinoma (EEC).
Methods: We analyzed ACOXL-AS1 expression and its association with clinical outcomes using pan-cancer RNA-seq data from TCGA and GTEx databases. Functional validation was performed in EEC cell lines (HHUA, HEC-1 A) via lentivirus-mediated overexpression, followed by CCK-8, colony formation, and transwell migration/invasion assays. Mechanistic insights were investigated using integrated bioinformatics approaches.
Results: ACOXL-AS1 was significantly downregulated in most cancers, and higher expression correlated with improved prognosis. Elevated ACOXL-AS1 levels were associated with smaller tumor size, lower disease stage, reduced metastasis, and decreased tumor mutational burden (TMB)/microsatellite instability (MSI). It also modulated the immunosuppressive tumor microenvironment. Critically, ACOXL-AS1 overexpression significantly inhibited EEC cell proliferation, migration, invasion, and tumor growth in xenograft models. Mechanistically, it may regulate RPA4 expression through the homologous recombination pathway in EEC cells.
Conclusions: ACOXL-AS1 may play a role as a tumor suppressor in endometrial endometrioid carcinoma (EEC), suggesting its potential as a prognostic biomarker and a candidate for further exploration as a therapeutic target.
期刊介绍:
BMC Cancer is an open access, peer-reviewed journal that considers articles on all aspects of cancer research, including the pathophysiology, prevention, diagnosis and treatment of cancers. The journal welcomes submissions concerning molecular and cellular biology, genetics, epidemiology, and clinical trials.