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- Title
MicroRNA-mediated downregulation of mTOR/FGFR3 controls tumor growth induced by Src-related oncogenic pathways.
- Authors
Oneyama, C; Ikeda, J; Okuzaki, D; Suzuki, K; Kanou, T; Shintani, Y; Morii, E; Okumura, M; Aozasa, K; Okada, M
- Abstract
The tyrosine kinase c-Src is upregulated in various human cancers, but the molecular mechanisms underlying c-Src-mediated tumor growth remain unclear. Here we examined the involvement of microRNAs in the c-Src-mediated tumor growth. Microarray profiling revealed that c-Src activation downregulates a limited set of microRNAs, including miR-99a, which targets oncogenic mammalian target of rapamycin (mTOR) and fibroblast growth factor receptor 3 (FGFR3). Re-expression of miR-99a suppressed tumor growth of c-Src-transformed cells, and this effect was restored by the overexpression of mTOR. The downregulation of miR-99a was also observed in epidermal growth factor- and Ras-transformed cells, and it was suppressed by inhibiting the mitogen-activated protein kinase (MAPK) pathway. Furthermore, miR-99a downregulation is associated with mTOR/FGFR3 upregulation in various human lung cancer cells/tissues. The tumorigenicity of these cells was suppressed by the introduction of miR-99a. These findings suggest that the miR-99a-mTOR/FGFR3 pathway is crucial for controlling tumor growth in a wide range of human cancers that harbor upregulation of the Src-related oncogenic pathways.
- Subjects
RNA; RAPAMYCIN; TUMOR growth; PROTEIN-tyrosine kinases; MICROARRAY technology; GENE expression; MITOGEN-activated protein kinases; CANCER cells
- Publication
Oncogene, 2011, Vol 30, Issue 32, p3489
- ISSN
0950-9232
- Publication type
Article
- DOI
10.1038/onc.2011.63