Unknown

Dataset Information

0

EGFR and MET receptor tyrosine kinase-altered microRNA expression induces tumorigenesis and gefitinib resistance in lung cancers.


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 ? (PKC-?) and sarcoma viral oncogene homolog (SRC). These findings suggest that modulation of specific miRNAs may provide a therapeutic approach for the treatment of NSCLCs.

SUBMITTER: Garofalo M 

PROVIDER: S-EPMC3467100 | biostudies-literature | 2011 Dec

REPOSITORIES: biostudies-literature

altmetric image

Publications


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 b  ...[more]

Similar Datasets

| S-EPMC2767331 | biostudies-literature
| S-EPMC2813301 | biostudies-literature
| S-EPMC5283661 | biostudies-literature
| S-EPMC5739624 | biostudies-literature
| S-EPMC3542232 | biostudies-literature
| S-EPMC3186869 | biostudies-literature
| S-EPMC3103760 | biostudies-literature
| S-EPMC2043012 | biostudies-literature
| S-EPMC4277244 | biostudies-literature
| S-EPMC7072161 | biostudies-literature