title: MicroRNA-34a overcomes HGF-mediated gefitinib resistance in EGFR mutant lung cancer cells partly by targeting MET.
abstract: In non-small-cell lung cancer (NSCLC) that harbours an activating epidermal growth factor receptor (EGFR) mutation, over-expression of hepatocyte growth factor (HGF) is an important mechanism involved in the acquired resistance to EGFR-tyrosine kinase inhibitors (TKIs) by restoring activity of the PI3K/Akt pathway via phosphorylation of MET. In our study, we found that the forced expression of miR-34a inhibited cell growth and induced apoptosis partly by targeting MET in HGF-induced gefitinib-resistant HCC827 and PC-9 cells. Furthermore, dramatic tumour regression was observed in the miR-34a plus gefitinib group in HGF-induced gefitinib resistant mouse xenograft models. This study demonstrates for the first time that miR-34a rescues HGF-induced gefitinib resistance in EGFR mutant NSCLC cells.
authors.affiliation: Department of Respiratory Diseases, Thoracic Disease Diagnosis and Treatment Center, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
authors.forename: Jian-Ya
authors.initials: JY
authors.lastname: Zhou
authors.affiliation: Department of Respiratory Diseases, Thoracic Disease Diagnosis and Treatment Center, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
authors.forename: Xi
authors.initials: X
authors.lastname: Chen
authors.affiliation: Department of Pathology, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Zhao
authors.affiliation: Department of Respiratory Diseases, Thoracic Disease Diagnosis and Treatment Center, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
authors.forename: Zhang
authors.initials: Z
authors.lastname: Bao
authors.affiliation: Department of Respiratory Diseases, Thoracic Disease Diagnosis and Treatment Center, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
authors.forename: Xing
authors.initials: X
authors.lastname: Chen
authors.affiliation: Department of Respiratory Diseases, Thoracic Disease Diagnosis and Treatment Center, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
authors.forename: Pei
authors.initials: P
authors.lastname: Zhang
authors.affiliation: PET Center, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
authors.forename: Zhen-Feng
authors.initials: ZF
authors.lastname: Liu
authors.affiliation: Department of Respiratory Diseases, Thoracic Disease Diagnosis and Treatment Center, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China. Electronic address: zjyhz@zju.edu.cn.
authors.forename: Jian-Ying
authors.initials: JY
authors.lastname: Zhou
mesh_terms: D020413:3' Untranslated Regions; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D048708:Cell Growth Processes / Q000187:drug effects; D045744:Cell Line, Tumor; D015536:Down-Regulation; D019008:Drug Resistance, Neoplasm; D066246:ErbB Receptors / Q000235:genetics* / Q000378:metabolism; D005260:Female; D000077156:Gefitinib; D017228:Hepatocyte Growth Factor / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D019859:Proto-Oncogene Proteins c-met / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism; D011799:Quinazolines / Q000494:pharmacology*; D011897:Random Allocation; D014162:Transfection; D023041:Xenograft Model Antitumor Assays
chemical_list: D020413:3' Untranslated Regions; D000970:Antineoplastic Agents; C066855:HGF protein, human; C522425:MIRN34 microRNA, human; D035683:MicroRNAs; D011799:Quinazolines; D017228:Hepatocyte Growth Factor; C512478:EGFR protein, human; D066246:ErbB Receptors; C491743:MET protein, human; D019859:Proto-Oncogene Proteins c-met; D000077156:Gefitinib
keywords: Gefitinib resistance; HGF; Lung cancer; MET; miR-34a