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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
32
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pubmed:dateCreated |
2011-8-11
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pubmed:databankReference |
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pubmed:abstractText |
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.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Aug
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pubmed:issn |
1476-5594
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pubmed:author |
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pubmed:issnType |
Electronic
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pubmed:day |
11
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pubmed:volume |
30
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
3489-501
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pubmed:meshHeading |
pubmed-meshheading:21383697-Animals,
pubmed-meshheading:21383697-Cell Line,
pubmed-meshheading:21383697-Cell Proliferation,
pubmed-meshheading:21383697-Cell Transformation, Neoplastic,
pubmed-meshheading:21383697-Cells, Cultured,
pubmed-meshheading:21383697-Cluster Analysis,
pubmed-meshheading:21383697-Down-Regulation,
pubmed-meshheading:21383697-Gene Expression Profiling,
pubmed-meshheading:21383697-HEK293 Cells,
pubmed-meshheading:21383697-Humans,
pubmed-meshheading:21383697-Immunoblotting,
pubmed-meshheading:21383697-Immunohistochemistry,
pubmed-meshheading:21383697-Lung Neoplasms,
pubmed-meshheading:21383697-Mice,
pubmed-meshheading:21383697-Mice, Inbred BALB C,
pubmed-meshheading:21383697-Mice, Nude,
pubmed-meshheading:21383697-MicroRNAs,
pubmed-meshheading:21383697-Neoplasms,
pubmed-meshheading:21383697-Pyrimidines,
pubmed-meshheading:21383697-RNA Interference,
pubmed-meshheading:21383697-Receptor, Fibroblast Growth Factor, Type 3,
pubmed-meshheading:21383697-Reverse Transcriptase Polymerase Chain Reaction,
pubmed-meshheading:21383697-Signal Transduction,
pubmed-meshheading:21383697-TOR Serine-Threonine Kinases,
pubmed-meshheading:21383697-src-Family Kinases
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pubmed:year |
2011
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pubmed:articleTitle |
MicroRNA-mediated downregulation of mTOR/FGFR3 controls tumor growth induced by Src-related oncogenic pathways.
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pubmed:affiliation |
Department of Oncogene Research, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka, Japan. coneyama@biken.osaka-u.ac.jp
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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