MicroRNA‑885‑5p regulates cell cycle progression in liver cancer cells.

Abstract

MicroRNAs (miRNAs) are small non‑coding RNAs that regulate gene expression by targeting messenger RNAs for translational repression or degradation. Dysregulation of miRNAs has been implicated in liver cancer development, including hepatocellular carcinoma (HCC). The present study identified miR‑885‑5p as a novel tumor-suppressor miRNA in liver cancer. Analysis of miRNA expression profiles from The Cancer Genome Atlas Program and Gene Expression Omnibus databases demonstrated a consistent downregulation of miR‑885‑5p in HCC tissues. Overexpression of miR‑885‑5p via lentiviral transduction significantly suppressed liver cancer cell proliferation, supporting its tumor‑suppressive role. To investigate the underlying mechanism, transcriptomic profiling of miR‑885‑5p‑overexpressing liver cancer cells was performed. Kyoto Encyclopedia of Genes and Genomes and Gene Ontology analyses highlighted the cell cycle as the most significantly affected pathway. Specifically, miR‑885‑5p downregulated key G₁/S transition‑promoting genes, including CDK6, E2F Transcription Factor 2 and Origin Recognition Complex Subunit 1 (ORC1), in liver cancer cells. To examine if miR‑885‑5p regulates the G1/S transition, a bromodeoxyuridine labeling assay and cell cycle analysis were performed. Corroborating the transcriptomic data, liver cancer cells with overexpressed miR‑885‑5p exhibited reduced bromodeoxyuridine incorporation and G₁ phase arrest. To gain further mechanistic insights, bioinformatics tools were used to predict gene targets of miR‑885‑5p in the G₁/S transition. Dual luciferase assays were conducted, which identified the direct interaction of miR‑885‑5p with the 3' untranslated regions of CDK6 and ORC1 messenger RNAs. Given its inhibitory effect on the G₁/S transition, the therapeutic potential of miR‑885‑5p was assessed. miR‑885‑5p overexpression sensitized liver cancer cells to the CDK4/6 inhibitors palbociclib, ribociclib and abemaciclib. The present findings collectively demonstrated that miR‑885‑5p induces cell cycle arrest and enhances CDK4/6 inhibitor sensitivity in liver cancer, suggesting its potential as a therapeutic target.