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Mol Pharm. 2018 Aug 6;15(8):3205-3215. doi: 10.1021/acs.molpharmaceut.8b00302. Epub 2018 Jun 28.

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

Shao Y1, Zhang D1,2, Li X1,2, Yang J1,2, Chen L1,2, Ning Z1, Xu Y1,2, Deng G1,2, Tao M2, Zhu Y2, Jiang J1,2.

Author information

1
Jiangsu Engineering Research Center for Tumor Immunotherapy , Changzhou 213003 , China.
2
Institute of Cell Therapy , Soochow University , Changzhou 213003 , China.

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.

KEYWORDS:

Bmi-1; hepatocellular carcinoma; miR-203; prognosis; radiosensitivity

[Indexed for MEDLINE]

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