MiR-133b reverses cisplatin resistance by targeting GSTP1 in cisplatin-resistant lung cancer cells

Abstract

MicroRNAs play a critical role in chemoresistance and are implicated in various biological and pathological processes of cells. The objective of the present study was to explore the role of miR-133b and its mechanism in the regulation of cisplatin resistance and tumor progression in cisplatin-resistant non-small cell lung cancer (NSCLC) cells. Reverse transcription-quantitative polymerase chain reaction and western blot assays of the cisplatin-resistant cell lines A549/DPP and H1299/DD P displayed the reduced expression of miR-133b and increased expression of glutathione-S-Transferase P1 (GSTP1) in the resistant cells compared with the respective parental cell lines A549 and H1299. Cell Counting kit-8, flow cytometry, colony formation and Transwell migration assays indicated that the overexpression of miR-133b increased the chemosensitivity to cisplatin and attenuated the proliferation and migration capacities of the cisplatin-resistant NSCLC cell lines in vitro. A dual-luciferase reporter assay demonstrated that miR-133b negatively regulated the expression of GSTP1 by targeting its 3'-untranslated region. In addition, the knockdown of GSTP1 by transfection with small interfering RNA exerted similar effects on cell chemosensitivity, proliferation and migration as did ectopic miR-133b expression, in addition to the upregulation of Bax and downregulation of Bcl-2, survivin and matrix metalloproteinase expression. In conclusion, the present study findings provide the insights that miR-133b reduces cisplatin resistance and its overexpression contributes to the suppression of the malignant growth and aggressiveness of cisplatin-resistant NSCLC cells by targeting GSTP1. This could potentially be exploited as a novel therapeutic strategy for the reversal of cisplatin resistance.