MicroRNA-203 Increases Cell Radiosensitivity via Directly Targeting Bmi-1 in Hepatocellular Carcinoma.

ABSTRACT

BACKGROUND: B-cell-specific moloney leukemia virus insertion site 1 (Bmi-1) plays important roles in various cancers, but its regulation through microRNAs (miRNAs) and its functions in hepatocellular carcinoma (HCC) remains unclear. METHODS: We evaluated the expression and prognostic significance of Bmi-1 in HCC by using tissue samples and The Cancer Genome Atlas (TCGA) data sets. The relationship between miRNAs and Bmi-1 was verified by bioinformatics prediction and immunofluorescence. Colony formation and apoptosis assays were used to reveal the effect of miR-203 on radiosensitivity. RESULTS: The Bmi-1 mRNA and protein were upregulated in HCC tissues. Cox regression multivariate analyses showed that Bmi-1 overexpression was an independent prognostic parameter for HCC patients. The expression level of Bmi-1 was negatively associated with miR-203 levels in HCC tissues. Dual-luciferase reporter assays showed that miR-203 could target the 3' untranslated region (3'-UTR) of Bmi-1 directly. Overexpression of miR-203 in HepG2 and Smmc-7721 cells increases their sensitivity to ionizing radiation in vitro and in vivo. Moreover, the improved cell radiosensitivity induced by miR-203 could be rescued by restoration of Bmi-1 expression. CONCLUSIONS: Bmi-1 could improve the predictive accuracy for HCC patients' survival. Moreover, miR-203 enhance cell radiosensitivity in vitro and in vivo by targeting Bmi-1 in HCC.