Up-regulation of miR-498 inhibits cell proliferation, invasion and migration of hepatocellular carcinoma by targeting FOXO3

Background: To unravel the fundamental role of miR-498 in the context of hepatocellular carcinoma cells and understands underlying potential mechanism.

Methods: Relative viability was interrogated using MTT method and cell proliferation was determined with colony formation assay. The protein levels of cleaved Caspase-3, Bcl-2, Cyclin D, CDK4, FOXO3 and β-actin were analyzed by western blotting. Cell invasion and migration was evaluated by transwell assay and wound healing, respectively. The relative abundance of Cyclin D, CDK4, FOXO3 and miR-498 transcripts was measured using real-time PCR. The regulatory action of miR-498 on FOXO3 expression was analyzed with luciferase reporter.

Results: Ectopic over-expression of miR-498 significantly inhibited viability and proliferation, suppressed cell migration and invasion, delayed cell cycle progression. We further identified FOXO3 as downstream target gene of miR-498, and positively modulated FOXO3 translation in miR-498-proficient cells consequently contributed to its anti-tumoral properties.

Conclusions: Our data highlighted the tumor suppressor role of miR-498-FOXO3 signaling in hepatocellular carcinoma cells, which might hold promise for therapeutic exploitation.