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miR-202 Enhances the Anti-Tumor Effect of Cisplatin on Non-Small Cell Lung Cancer by Targeting the Ras/MAPK Pathway

Authors
  • Sun, Wei
  • Ping, Wei
  • Tian, Yitao
  • Zou, Wenbin
  • Liu, Jiawei
  • Zu, Yukun
Type
Published Article
Journal
Cellular Physiology and Biochemistry
Publisher
S. Karger AG
Publication Date
Dec 06, 2018
Volume
51
Issue
5
Pages
2160–2171
Identifiers
DOI: 10.1159/000495835
PMID: 30522099
Source
Karger
Keywords
License
Green
External links

Abstract

Background/Aims: KRas is usually mutated in non-small cell lung cancer (NSCLC). The mutated KRas gene is a negative prognostic indicator that promotes tumor proliferation, metastasis, and drug resistance in NSCLC, and thus has become a target for cancer therapy. This study is focused on the effects of the microRNA (miR)-202/KRas axis in regulating chemosensitivity in NSCLC. Methods: Quantitative reverse transcriptase real-time PCR analysis was performed to examine the expression of miR-202. MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assays were performed to evaluate the sensitivity of cisplatin against NSCLC cells. The miR-202/KRas axis was confirmed by western blot and luciferase reporter assays. Cell apoptosis was measured by flow cytometry. KRas expression, MEK1/2 and ERK1/2 phosphorylation, and activation of caspase-9 and caspase-3 were detected by western blot. Results: A significant decrease in miR-202 expression was observed in NSCLC cells both in vivo and in vitro. In addition, miR-202 expression was associated with drug resistance. Recovery of miR-202 expression levels was found to increase the sensitivity of both NCI-H441 and A549 NSCLC cells to cisplatin treatment. Mechanically, as the Ras/mitogen-activated protein kinase (MAPK) pathway was aberrantly activated in NCI-H441 and A549 NSCLC cells, the overexpression of miR-202 was found to inhibit the Ras/MAPK pathway by targeting the KRas gene. As a result, increased miR-202 expression expanded apoptosis signaling induced by cisplatin in NSCLC cells. Conclusion: The miR-202/KRas axis controlled the chemosensitivity of NSCLC by mediating the Ras/MAPK pathway. Thus, the combination of platinum-based drugs with miR-202 may represent a novel strategy to enhance the anti-tumor effect against NSCLC.

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