EGFR and MET receptor tyrosine kinase-altered microRNA expression induces tumorigenesis and gefitinib resistance in lung cancers
2012
Online
academicJournal
Zugriff:
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.
Titel: |
EGFR and MET receptor tyrosine kinase-altered microRNA expression induces tumorigenesis and gefitinib resistance in lung cancers
|
---|---|
Autor/in / Beteiligte Person: | Garofalo, Michela ; Romano, Giulia ; Di Leva, Gianpiero ; Nuovo, Gerard ; Jeon, Young-Jun ; Ngankeu, Apollinaire ; Sun, Jin ; Lovat, Francesca ; Alder, Hansjuerg ; Condorelli, Gerolama ; Engelman, Jeffrey Adam ; Ono, Mayumi ; Rho, Jin Kyung ; Cascione, Luciano ; Volinia, Stefano ; Nephew, Kenneth P. ; Croce, Carlo M. |
Link: | |
Veröffentlichung: | 2012 |
Medientyp: | academicJournal |
ISSN: | 1078-8956 (print) |
DOI: | 10.1038/nm.2577 |
Sonstiges: |
|