Open AccessmiR‐1‐3p and miR‐206 sensitizes HGF ‐induced gefitinib‐resistant human lung cancer cells through inhibition of c‐Met signalling and EMT
Author(s) -
Jiao Demin,
Chen Jun,
Li Yu,
Tang Xiali,
Wang Jian,
Xu Wei,
Song Jia,
Li You,
Tao Huimin,
Chen Qingyong
Publication year - 2018
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.13629
Subject(s) - gefitinib , hepatocyte growth factor , epidermal growth factor receptor , lung cancer , cancer research , gene knockdown , protein kinase b , mapk/erk pathway , metastasis , c met , medicine , signal transduction , cancer , chemistry , biology , receptor , oncology , cell culture , microbiology and biotechnology , genetics
Hepatocyte growth factor ( HGF ) overexpression is an important mechanism in acquired epidermal growth factor receptor ( EGFR ) kinase inhibitor gefitinib resistance in lung cancers with EGFR activating mutations. MiR‐1‐3p and miR‐206 act as suppressors in lung cancer proliferation and metastasis. However, whether miR‐1‐3p and miR‐206 can overcome HGF ‐induced gefitinib resistance in EGFR mutant lung cancer is not clear. In this study, we showed that miR‐1‐3p and miR‐206 restored the sensitivities of lung cancer cells PC ‐9 and HCC ‐827 to gefitinib in present of HGF . For the mechanisms, we demonstrated that both miR‐1‐3p and miR‐206 directly target HGF receptor c‐Met in lung cancer. Knockdown of c‐Met mimicked the effects of miR‐1‐3p and miR‐206 transfections Meanwhile, c‐Met overexpression attenuated the effects of miR‐1‐3p and miR‐206 in HGF ‐induced gefitinib resistance of lung cancers. Furthermore, we showed that miR‐1‐3p and miR‐206 inhibited c‐Met downstream Akt and Erk pathway and blocked HGF ‐induced epithelial‐mesenchymal transition ( EMT ). Finally, we demonstrated that miR‐1‐3p and miR‐206 can increase gefitinib sensitivity in xenograft mouse models in vivo . Our study for the first time indicated the new function of miR‐1‐3p and miR‐206 in overcoming HGF ‐induced gefitinib resistance in EGFR mutant lung cancer cell.