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

Lin,Chen; Xie,Liyi; Lu,Yan; Hu,Zhihuang; Chang,Jianhua

doi:10.3892/ijmm.2018.3382

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

Authors:
- Chen Lin
- Liyi Xie
- Yan Lu
- Zhihuang Hu
- Jianhua Chang
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Affiliations: Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, P.R. China
Published online on: January 11, 2018 https://doi.org/10.3892/ijmm.2018.3382
Pages: 2050-2058
Copyright: © Lin et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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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/DDP 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.

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