MicroRNA‑506‑3p reverses gefitinib resistance in non‑small cell lung cancer by targeting Yes‑associated protein 1

Zhu,Junfei; Tao,Lianqin; Jin,Litong

doi:10.3892/mmr.2018.9710

MicroRNA‑506‑3p reverses gefitinib resistance in non‑small cell lung cancer by targeting Yes‑associated protein 1

Authors:
- Junfei Zhu
- Lianqin Tao
- Litong Jin
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Affiliations: Department of Respiratory Medicine, Taizhou Central Hospital, Taizhou, Zhejiang 318000, P.R. China, Department of Emergency, Taizhou Central Hospital, Taizhou, Zhejiang 318000, P.R. China
Published online on: November 29, 2018 https://doi.org/10.3892/mmr.2018.9710
Pages: 1331-1339

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Abstract

Epidermal growth factor receptor‑tyrosine kinase inhibitors, such as gefitinib, have been found to be clinically effective in the treatment of patients with non‑small cell lung cancer (NSCLC). However, the therapeutic effect of gefitinib is often limited by the development of gefitinib resistance. MicroRNAs (miRNAs), a group of small non‑coding RNAs, have been demonstrated to be frequently dysregulated in human malignancies. For instance, the downregulation of miR‑506‑3p has been reported in NSCLC patients. The aim of the present study was to determine the role and underlying molecular mechanism of miR‑506‑3p in the regulation of gefitinib sensitivity in NSCLC. A gefitinib‑resistant PC‑9 (PC‑9GR) cell line was established, and reduced miR‑506‑3p expression was observed in PC‑9GR cells as compared with that in parental cells. The results of cell cytotoxicity and cell apoptosis assays indicated that PC‑9GR cells were more sensitive to gefitinib following the transfection with an miR‑506‑3p mimic, while transfection with an miR‑506‑3p antagonist reduced the sensitivity of PC‑9GR cells to gefitinib. It was further revealed that Yes‑associated protein 1 (YAP1) was directly suppressed by miR‑506‑3p in PC‑9GR cells. The elevated sensitivity of PC‑9GR cells to gefitinib following transfection with the miR‑506‑3p mimic was counteracted by the overexpression of YAP1. Furthermore, an inverse correlation between the miR‑506‑3p and YAP1 mRNA levels was detected in lung adenocarcinoma specimens. Collectively, the results of the present study suggested that the downregulation of miR‑506‑3p contributes to gefitinib resistance, and thus, the restoration of miR‑506‑3p may be a potential therapeutic approach for overcoming NSCLC gefitinib resistance.

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