EGFR and MET receptor tyrosine kinase-altered microRNA expression induces tumorigenesis and gefitinib resistance in lung cancers
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Author
Garofalo, Michela
Romano, Giulia
Di Leva, Gianpiero
Nuovo, Gerard
Jeon, Young-Jun
Ngankeu, Apollinaire
Sun, Jin
Lovat, Francesca
Alder, Hansjuerg
Condorelli, Gerolama
Ono, Mayumi
Rho, Jin Kyung
Cascione, Luciano
Volinia, Stefano
Nephew, Kenneth P.
Croce, Carlo M.
Note: Order does not necessarily reflect citation order of authors.
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https://doi.org/10.1038/nm.2577Metadata
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Garofalo, 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.Abstract
The 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.Other Sources
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3467100/pdf/Terms of Use
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