title: Down-regulation of miR-214 reverses erlotinib resistance in non-small-cell lung cancer through up-regulating LHX6 expression.
abstract: Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are standard treatments for advanced non-small-cell lung cancer (NSCLC) patients. However, acquired resistance to EGFR-TKIs is widely detected across the world, and the exact mechanisms have not been fully demonstrated until now. This study aimed to examine the role of miR-214 in the acquired resistance to erlotinib in NSCLC, and elucidate the underlying mechanisms. qRT-PCR assay detected higher miR-214 expression in the plasma of NSCLC patients with acquired EGFR-TKI resistance than prior to EGFR-TKI therapy, and in the generated erlotinib-resistant HCC827 (HCC827/ER) cells than in HCC827 cells. Bioinformatics analysis and dual-luciferase reporter assay indentified LHX6 as a direct target gene of miR-214, and LHX6 expression was detected to be down-regulated in erlotinib-resistant HCC827 cells. Transwell invasion assay revealed that overexpressing LHX6 reversed the increase in the invasive ability of HCC827 cells induced by miR-214 overexpression, and the CRISPR-Cas9 system-mediated LHX6 knockdown reversed the reduction in the invasion of erlotinib-resistant HCC827 cells caused by miR-214 down-regulation. The results of the present study demonstrate that down-regulation of miR-214 may reverse acquired resistance to erlotinib in NSCLC through mediating its direct target gene LHX6 expression.
authors.affiliation: Department of Radiobiology, Fujian Cancer Hospital, Fujian Medical University Cancer Hospital, Fuzhou, 350014, Fujian Province, P.R. China.
authors.forename: Jinrong
authors.initials: J
authors.lastname: Liao
authors.affiliation: Department of Thoracic Medical Oncology, Fujian Cancer Hospital, Fujian Medical University Cancer Hospital, Fuzhou, 350014, Fujian Province, P.R. China.
authors.forename: Jinghui
authors.initials: J
authors.lastname: Lin
authors.affiliation: Department of Thoracic Medical Oncology, Fujian Cancer Hospital, Fujian Medical University Cancer Hospital, Fuzhou, 350014, Fujian Province, P.R. China.
authors.forename: Dong
authors.initials: D
authors.lastname: Lin
authors.affiliation: Department of Radiobiology, Fujian Cancer Hospital, Fujian Medical University Cancer Hospital, Fuzhou, 350014, Fujian Province, P.R. China.
authors.forename: Changyan
authors.initials: C
authors.lastname: Zou
authors.affiliation: Department of Molecular and Cellular Biology, Irell & Manella Graduate School of Biological Sciences, Beckman Research Institute of the City of Hope, Duarte, CA, 91010, USA.
authors.forename: Jessica
authors.initials: J
authors.lastname: Kurata
authors.affiliation: Department of Molecular and Cellular Biology, Irell & Manella Graduate School of Biological Sciences, Beckman Research Institute of the City of Hope, Duarte, CA, 91010, USA.
authors.forename: Renjang
authors.initials: R
authors.lastname: Lin
authors.affiliation: Department of Thoracic Medical Oncology, Fujian Cancer Hospital, Fujian Medical University Cancer Hospital, Fuzhou, 350014, Fujian Province, P.R. China. zhiyonghecn@sina.com.
authors.forename: Zhiyong
authors.initials: Z
authors.lastname: He
authors.affiliation: Department of Radiobiology, Fujian Cancer Hospital, Fujian Medical University Cancer Hospital, Fuzhou, 350014, Fujian Province, P.R. China. zjsuying@hotmail.com.
authors.forename: Ying
authors.initials: Y
authors.lastname: Su
mesh_terms: D020413:3' Untranslated Regions; D000970:Antineoplastic Agents / Q000494:pharmacology; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics*; D045744:Cell Line, Tumor; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D066246:ErbB Receptors / Q000235:genetics; D000069347:Erlotinib Hydrochloride / Q000494:pharmacology*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D060850:LIM-Homeodomain Proteins / Q000235:genetics*; D008175:Lung Neoplasms / Q000235:genetics*; D035683:MicroRNAs / Q000235:genetics*; D009419:Nerve Tissue Proteins / Q000235:genetics*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D034622:RNA Interference; D014157:Transcription Factors / Q000235:genetics*
chemical_list: D020413:3' Untranslated Regions; D000970:Antineoplastic Agents; C121947:LHX6 protein, human; D060850:LIM-Homeodomain Proteins; C547397:MIRN214 microRNA, human; D035683:MicroRNAs; D009419:Nerve Tissue Proteins; D047428:Protein Kinase Inhibitors; D014157:Transcription Factors; D000069347:Erlotinib Hydrochloride; D066246:ErbB Receptors