MicroRNA-885-5p regulates cell cycle progression in hepatocellular carcinoma cells

MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression by targeting messenger RNA (mRNA) for translational repression or degradation. Dysregulation of miRNAs has been implicated in hepatocellular carcinoma (HCC) development. Here, we identify miR-885-5p as a novel tumor suppressor miRNA in HCC. Analysis of miRNA expression profiles from TCGA and GEO databases revealed downregulation of miR-885-5p in HCC tissues. Overexpression of miR-885-5p significantly suppressed HCC cell proliferation, supporting its tumor-suppressive role. Transcriptomic profiling of miR-885-5p-overexpressing HCC cells identified cell cycle as the most affected pathway by KEGG and GO analyses. Specifically, miR-885-5p induced downregulation of G1/S transition-promoting genes, including CDK6, E2F2, and CCNA2, in HCC cells. Consequently, these cells exhibited reduced BrdU incorporation and G1 phase arrest. Dual luciferase assays confirmed direct interaction of miR-885-5p with the 3' untranslated regions of CDK6, E2F2, and CCNA2 mRNAs. Furthermore, miR-885-5p overexpression sensitized HCC cells to the CDK4/6 inhibitors palbociclib, ribociclib, and abemaciclib. These findings demonstrate that miR-885-5p induces cell cycle arrest and enhances CDK4/6 inhibitor sensitivity in HCC, suggesting its potential as a therapeutic target.