Garofalo, MichelaRomano, GiuliaDi Leva, GianpieroNuovo, GerardJeon, Young-JunNgankeu, ApollinaireSun, JinLovat, FrancescaAlder, HansjuergCondorelli, GerolamaEngelman, Jeffrey AOno, MayumiRho, Jin KyungCascione, LucianoVolinia, StefanoNephew, Kenneth P.Croce, Carlo M.2013-04-152012Garofalo, Michela, Giulia Romano, Gianpiero Di Leva, Gerard Nuovo, Young-Jun Jeon, Apollinaire Ngankeu, Jin Sun, et al. 2012. EGFR and MET receptor tyrosine kinase-altered microRNA expression induces tumorigenesis and gefitinib resistance in lung cancers. Nature Medicine 18(1): 74-82.1078-8956http://nrs.harvard.edu/urn-3:HUL.InstRepos:10531918The involvement of the MET oncogene in de novo and acquired resistance of non-small cell lung cancers (NSCLC) to tyrosine kinase inhibitors (TKIs) has been reported, but the precise mechanism by which MET overexpression contributes to TKI-resistant NSCLC remains unclear. MicroRNAs (miRNAs) negatively regulate gene expression and their dysregulation has been implicated in tumorigenesis. To understand the role of microRNAs in TKI-resistant NSCLC, we examined TK receptor-mediated microRNA changes. Here we report that miR-30b/c and miR-221/222, modulated by both EGF and MET receptors, and miR-103, -203, controlled only by MET, play important roles in gefitinib-induced apoptosis and epithelial-mesenchymal transition (EMT) of NSCLC cells, in vitro and in vivo, by inhibiting the expression of Bim, APAF-1, PKC-ε and SRC genes. The finding suggests that modulation of specific microRNAs may provide a therapeutic approach for future treatment of NSCLC.en-USJournal Article2013-04-1510.1038/nm.2577