RETRACTED ARTICLE: EGFR and MET receptor tyrosine kinase–altered microRNA expression induces tumorigenesis and gefitinib resistance in lung cancers

M Garofalo, G Romano, G Di Leva, G Nuovo, YJ Jeon… - Nature medicine, 2012 - nature.com
M Garofalo, G Romano, G Di Leva, G Nuovo, YJ Jeon, A Ngankeu, J Sun, F Lovat, H Alder…
Nature medicine, 2012nature.com
The involvement of the MET oncogene in de novo and acquired resistance of non-small cell
lung cancers (NSCLCs) to tyrosine kinase inhibitors (TKIs) has previously 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 their role in TKI-resistant
NSCLCs, we examined changes in miRNA that are mediated by tyrosine kinase receptors …
Abstract
The involvement of the MET oncogene in de novo and acquired resistance of non-small cell lung cancers (NSCLCs) to tyrosine kinase inhibitors (TKIs) has previously 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 their role in TKI-resistant NSCLCs, we examined changes in miRNA that are mediated by tyrosine kinase receptors. Here we report that miR-30b, miR-30c, miR-221 and miR-222 are modulated by both epidermal growth factor (EGF) and MET receptors, whereas miR-103 and miR-203 are controlled only by MET. We showed that these miRNAs have important roles in gefitinib-induced apoptosis and epithelial-mesenchymal transition of NSCLC cells in vitro and in vivo by inhibiting the expression of the genes encoding BCL2-like 11 (BIM), apoptotic peptidase activating factor 1 (APAF-1), protein kinase C ɛ (PKC-ɛ) and sarcoma viral oncogene homolog (SRC). These findings suggest that modulation of specific miRNAs may provide a therapeutic approach for the treatment of NSCLCs.
nature.com