期刊
INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE
卷 41, 期 4, 页码 2050-2058出版社
SPANDIDOS PUBL LTD
DOI: 10.3892/ijmm.2018.3382
关键词
miR-133b; cisplatin resistance; proliferation; migration; GSTP1; non-small cell lung cancer
资金
- Shanghai Science and Technology Committee [124119a6200]
- National Natural Science Foundation of China [81401896]
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 down-regulation 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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