title: miR-124 modulates gefitinib resistance through SNAI2 and STAT3 in non-small cell lung cancer.
abstract: 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 miR-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 miR-124 depletion induced gefitinib resistance, and miR-124 overexpression sensitized gefitinib-resistant cells to gefitinib. Mechanistic analysis revealed that miR-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 miR-124 depletion. Our data demonstrate that the miR-124 plays a new critical role in acquired resistance to gefitinib and that the manipulation of miR-124 might provide a therapeutic strategy for reversing acquired gefitinib resistance.
authors.affiliation: Cancer Research Institute, Huazhong University of Science and Technology, Wuhan, 430030, China.
authors.forename: Fa-Yong
authors.initials: FY
authors.lastname: Hu
authors.affiliation: Department of Thoracic Surgery, Huazhong University of Science and Technology, Wuhan, 430030, China.
authors.forename: Xiao-Nian
authors.initials: XN
authors.lastname: Cao
authors.affiliation: Department of Thoracic Surgery, Huazhong University of Science and Technology, Wuhan, 430030, China.
authors.forename: Qin-Zi
authors.initials: QZ
authors.lastname: Xu
authors.affiliation: Department of Thoracic Surgery, Huazhong University of Science and Technology, Wuhan, 430030, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Deng
authors.affiliation: Cancer Research Institute, Huazhong University of Science and Technology, Wuhan, 430030, China.
authors.forename: Sen-Yan
authors.initials: SY
authors.lastname: Lai
authors.affiliation: Department of Respiratory and Critical Care Medicine, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, 430030, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Ma
authors.affiliation: Cancer Research Institute, Huazhong University of Science and Technology, Wuhan, 430030, China. jbhu@tjh.tjmu.edu.cn.
authors.forename: Jun-Bo
authors.initials: JB
authors.lastname: Hu
mesh_terms: D020413:3' Untranslated Regions; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism; D045744:Cell Line, Tumor; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D000077156:Gefitinib; D057809:HEK293 Cells; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism; D035683:MicroRNAs / Q000235:genetics*; D011799:Quinazolines / Q000494:pharmacology / Q000627:therapeutic use*; D050796:STAT3 Transcription Factor / Q000235:genetics / Q000378:metabolism; D000071250:Snail Family Transcription Factors / Q000235:genetics / Q000378:metabolism
chemical_list: D020413:3' Untranslated Regions; D000970:Antineoplastic Agents; C509207:MIRN124 microRNA, human; D035683:MicroRNAs; D011799:Quinazolines; C000604408:SNAI2 protein, human; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D000071250:Snail Family Transcription Factors; D000077156:Gefitinib
keywords: SNAI2; STAT3; gefitinib-resistance; miR-124; non-small cell lung cancer