miR-1-3p and miR-206 sensitizes HGF-induced gefitinib-resistant human lung cancer cells through inhibition of c-Met signalling and EMT.

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.
PMID: 29664235 [PubMed - as supplied by publisher]

Source: J Cell Mol Med - April 17, 2018 Category: Molecular Biology Authors: Jiao D, Chen J, Li Y, Tang X, Wang J, Xu W, Song J, Li Y, Tao H, Chen Q Tags: J Cell Mol Med Source Type: research