EGFR and MET receptor tyrosine kinase-altered microRNA expression induces tumorigenesis and gefitinib resistance in lung cancers
| Autor: | Garofalo, M., Romano, G., Leva, G. D., Nuovo, G., Jeon, Y., Ngankeu, A., Sun, J., Lovat, F., Alder, H., Condorelli, G., Engelman, J. A., Ono, M., Rho, J. K., Cascione, L., Volinia, Stefano, Nephew, K. P., Croce, Carlo Maria |
|---|---|
| Přispěvatelé: | Garofalo, Michela, Romano, G., Di Leva, G., Nuovo, G., Jeon, Y. J., Ngankeu, A., Sun, J., Lovat, F., Alder, H., Condorelli, Gerolama, Engelman, J. A., Ono, M., Rho, J. K., Cascione, L., Volinia, S., Nephew, K. P., Croce, C. M. |
| Jazyk: | angličtina |
| Rok vydání: | 2011 |
| Předmět: | |
| Zdroj: | Nature medicine |
| ISSN: | 1546-170X 1078-8956 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|