ACOXL-AS1's pan-cancer dynamics and its proliferative impact on endometrial endometrioid carcinoma

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).

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.

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.

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.