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

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.

MicroRNA‑202 inhibits endometrial stromal cell migration and invasion by suppressing the K‑Ras/Raf1/MEK/ERK signaling pathway

“…K-Ras is one of the three members of the Ras oncogene family that has been previously implicated in the carcinogen-esis of many human cancers, where K-Ras knockdown has been shown to suppress tumor cell growth and invasion ( 47 , 48 ). Recently, a number of miRNAs, including miR-202, were reported to suppress K-Ras expression and functioned as a tumor suppressor ( 49 ). The present study found that K-Ras knockdown conferred an inhibitory effect on the invasion and migration of ESCs.…”

Retracted: Synthesis, Crystal Structures, and Anti‐cervical Cancer Activity Evaluation of Three Trinuclear Transition Metal(II) Complexes with N,O‐Donor Schiff Base Ligand

“…Western Blot Detection: Western blot detection was performed as described in detail . In brief, the Hela cells were exposed to different concentrations of tested nano 1 – 3 for 24 h, then the cells were harvested and lysed with the cell lysis buffer [1 % NP‐40, 1 % sodium dodecyl sulfate (SDS), 150 mM NaCl, 25 mM Tris‐HCl (pH 7.6), 1 % deoxycholic acid sodium salt, 1 % PMSF] for 30 min on the ice.…”

Machine Learning Identifies the miR-196b and miR-34c-5p as the Chemotherapy Response Biomarkers of Lung Adenocarcinoma

“…For instance, overexpression of miR-1 increases the chemosensitivity of non-small cell lung cancer cells by inhibiting autophagy (33). Furthermore, overexpression of miR-202 promotes chemosensitivity by suppressing the KRAS gene in lung adenocarcinoma (34). Notably, there also is increasing evidences that circulating miRNAs may be potential biomarkers for early diagnosis and prognosis of lung cancer (35,36).…”