Open AccessDown-regulation of miR-214 reverses erlotinib resistance in non-small-cell lung cancer through up-regulating LHX6 expression
Author(s) -
Jinrong Liu,
Jinghui Lin,
Lin Dong,
Changyan Zou,
Jessica Kurata,
RenJang Lin,
He Zhou,
Ying Su
Publication year - 2017
Publication title -
scientific reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.24
H-Index - 213
ISSN - 2045-2322
DOI - 10.1038/s41598-017-00901-6
Subject(s) - erlotinib , cancer research , epidermal growth factor receptor , gene knockdown , lung cancer , erlotinib hydrochloride , reporter gene , biology , medicine , cancer , gene expression , gene , oncology , genetics
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.