miR-124 Modulates Gefitinib Resistance through SNAI2 and STAT3 in Non-small Cell Lung Cancer

• Published in: Journal of Huazhong University of Science and Technology. Medical sciences Vol. 36; no. 6; pp. 839 - 845
• Main Author: 胡发涌 曹小年 徐沁孜 邓豫 来森艳 马静 胡俊波
• Format: Journal Article
• Language: English
• Published: Wuhan Huazhong University of Science and Technology 01.12.2016; Cancer Research Institute, Tongji Hospital Huazhong University of Science and Technology, Wuhan 430030, China%Department of Thoracic Surgery, Tongji Hospital Huazhong University of Science and Technology, Wuhan 430030, China%Department of Respiratory and Critical Care Medicine, Tongji Hospital Huazhong University of Science and Technology, Wuhan 430030, China
• Subjects: 3' Untranslated Regions; Antineoplastic Agents - pharmacology; Antineoplastic Agents - therapeutic use; Carcinoma, Non-Small-Cell Lung - drug therapy; Carcinoma, Non-Small-Cell Lung - genetics; Carcinoma, Non-Small-Cell Lung - metabolism; Cell Line, Tumor; Drug Resistance, Neoplasm - genetics; HEK293 Cells; Humans; Lung Neoplasms - drug therapy; Lung Neoplasms - genetics; Lung Neoplasms - metabolism; Medicine; Medicine & Public Health; MicroRNAs - genetics; Quinazolines - pharmacology; Quinazolines - therapeutic use; Snail Family Transcription Factors - genetics; Snail Family Transcription Factors - metabolism; STAT3 Transcription Factor - genetics; STAT3 Transcription Factor - metabolism; miR-124; non-small cell lung cancer; SNAI2; gefitinib-resistance; STAT3
• ISSN: 1672-0733; 1993-1352; 1993-1352
• DOI: 10.1007/s11596-016-1672-x

Gefitinib is used as a first-line treatment for advanced non-small cell lung cancer（NSCLC）.Unfortunately,most NSCLC patients inevitably develop gefitinib resistance during treatment.In addition to EGFR mutation status,the mechanisms involved are largely unknown.In this study,we showed that mi R-124,a tumor suppressor,was significantly down-regulated in gefitinib-resistant NSCLC patients and cell lines compared with gefitinib-sensitive patients and cell lines.In addition,the mi R-124 depletion induced gefitinib resistance,and mi R-124 overexpression sensitized gefitinib-resistant cells to gefitinib.Mechanistic analysis revealed that mi R-124 decreased SNAI2 and STAT3 expression by directly targeting their 3＇UTRs and that knocking down SNAI2 or STAT3 partly reversed the gefitinib resistance induced by mi R-124 depletion.Our data demonstrate that the mi R-124 plays a new critical role in acquired resistance to gefitinib and that the manipulation of mi R-124 might provide a therapeutic strategy for reversing acquired gefitinib resistance.