miRNA-195 sensitizes human hepatocellular carcinoma cells to 5-FU by targeting BCL-w
Affiliations: Institute of Pharmacy and Pharmacology, University of South China, 28 Changsheng Road, Hengyang, Hunan 421001, P.R. China, College of Pharmacy and Life Science, University of South China, 28 Changsheng Road, Hengyang, Hunan 421001, P.R. China
- Published online on: September 22, 2011 https://doi.org/10.3892/or.2011.1472
- Pages: 250-257
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The role of microRNA-195 in developing acquired drug resistance in hepatocellular carcinoma cells was investigated. Expression proﬁling of miRNAs revealed a limited set of miRNAs with altered expression in drug resistant hepatocellular carcinoma cell line BEL-7402/5-FU compared to its parental BEL-7402 cell line. Real-time PCR confirmed down-regulation of miRNA-195 in BEL-7402/5-FU cells. Overexpression of miRNA-195 sensitized BEL-7402/5-FU cells to anticancer drugs. Consistent with these findings, miR-195 antisense oligonucleotide induced drug resistance in BEL-7402/5-FU cells. Also, the basal levels of the anti-apoptotic protein Bcl-w were high in BEL-7402/5-FU cells and miR-195 overexpression repressed Bcl-w protein level and inhibited the luciferase activity of a Bcl-w 3' untranslated region-based reporter construct in both BEL-7402/5-FU and BEL-7402 cells. These results indicate that miR-195 could improve the drug sensitivity at least in part by targeting Bcl-w to increase cell apoptosis in hepatocellular carcinoma cells.