miR-885-3p promotes hepatocellular carcinoma metastasis by targeting TASP1 to stabilize HIF-1α and activate hypoxia-driven angiogenic and invasive programs.

backgroundHepatocellular carcinoma (HCC) progression is strongly influenced by hypoxia-driven HIF-1α signaling, which promotes EMT, invasion, angiogenesis, and metabolic adaptation. This study investigated whether miR-885-3p regulates HCC malignant phenotypes through the TASP1/HIF-1α axis.

methodsHuh7 cells were transfected with miR-885-3p mimic, inhibitor, or controls. RT-qPCR, Western blotting, immunofluorescence, and dual-luciferase reporter assays were performed to assess miR-885-3p, TASP1, and HIF-1α regulation. Functional assays evaluated EMT, migration, invasion, angiogenesis, oxidative stress, metabolism, colony formation, adhesion, focal adhesion formation, and cytoskeletal remodeling. TASP1 restoration was used to test rescue effects. GEO datasets and 30 HCC patient samples were analyzed for clinical correlations.

resultsHypoxia increased miR-885-3p expression and enhanced HIF-1α nuclear accumulation. miR-885-3p directly targeted the TASP1 3'-UTR, suppressed TASP1 expression, and promoted HIF-1α activation. miR-885-3p overexpression induced EMT, migration, invasion, angiogenesis, oxidative stress, glycolytic activity, clonogenicity, adhesion, and F-actin remodeling, whereas miR-885-3p inhibition produced opposite effects. TASP1 restoration reduced HIF-1α activation and partially reversed migration, invasion, and angiogenesis. Clinical analyses showed inverse correlations between miR-885-3p and TASP1 and positive correlations with VIM, VEGFA, MMP2, and HMOX1.

conclusionmiR-885-3p promotes HCC malignant phenotypes partly by targeting TASP1 and activating HIF-1α-associated signaling. Further in vivo validation is required.