Document Detail

MicroRNA-205 inhibits Src-mediated oncogenic pathways in renal cancer.
MedLine Citation:
PMID:  21330408     Owner:  NLM     Status:  MEDLINE    
The Src family of protein kinases (SFK) plays key roles in regulating fundamental cellular processes, including cell growth, differentiation, cell shape, migration, and survival, and specialized cell signals in various malignancies. The pleiotropic functions of SFKs in cancer make them promising targets for intervention. Here, we sought to investigate the role of microRNA-205 (miR-205) in inhibition of Src-mediated oncogenic pathways in renal cancer. We report that expression of miR-205 was significantly suppressed in renal cancer cell lines and tumors when compared with normal tissues and a nonmalignant cell line and is correlated inversely with the expression of SFKs. miR-205 significantly suppressed the luciferase activity of reporter plasmids containing the 3'-UTR (untranslated region) sequences complementary to either Src, Lyn, or Yes, which was abolished by mutations in these 3'-UTR regions. Overexpression of miR-205 in A498 cells reduced Src, Lyn, and Yes expression, both at mRNA and protein levels. Proliferation of renal cancer cells was suppressed by miR-205, mediated by the phospho-Src-regulated ERK1/2 pathway. Cell motility factor FAK (focal adhesion kinase) and STAT3 activation were also inhibited by miR-205. Transient and stable overexpression of miR-205 in A498 cells resulted in induction of G₀/G₁ cell-cycle arrest and apoptosis, as indicated by decreased levels of cyclin D1 and c-Myc, suppressed cell proliferation, colony formation, migration, and invasion in renal cancer cells. miR-205 also inhibited tumor cell growth in vivo. This is the first study showing that miR-205 inhibits proto-oncogenic SFKs, indicating a therapeutic potential of miR-205 in the treatment of renal cancer.
Shahana Majid; Sharanjot Saini; Altaf A Dar; Hiroshi Hirata; Varahram Shahryari; Yuichiro Tanaka; Soichiro Yamamura; Koji Ueno; Mohd Saif Zaman; Kamaldeep Singh; Inik Chang; Guoren Deng; Rajvir Dahiya
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, Non-P.H.S.     Date:  2011-02-17
Journal Detail:
Title:  Cancer research     Volume:  71     ISSN:  1538-7445     ISO Abbreviation:  Cancer Res.     Publication Date:  2011 Apr 
Date Detail:
Created Date:  2011-04-04     Completed Date:  2011-07-11     Revised Date:  2014-04-23    
Medline Journal Info:
Nlm Unique ID:  2984705R     Medline TA:  Cancer Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2611-21     Citation Subset:  IM    
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MeSH Terms
Apoptosis / physiology
Carcinoma, Renal Cell / enzymology,  genetics,  metabolism*
Cell Cycle / physiology
Cell Growth Processes / physiology
Cell Line, Tumor
Cell Movement / physiology
Kidney Neoplasms / enzymology,  genetics,  metabolism*
MAP Kinase Signaling System
MicroRNAs / biosynthesis*,  genetics
Mitogen-Activated Protein Kinase 1 / metabolism
Mitogen-Activated Protein Kinase 3 / metabolism
Proto-Oncogene Proteins c-yes / genetics
RNA, Small Interfering / administration & dosage,  genetics
raf Kinases / metabolism
ras Proteins / metabolism
src-Family Kinases / antagonists & inhibitors*,  genetics,  metabolism
Grant Support
Reg. No./Substance:
0/MIRN205 microRNA, human; 0/MicroRNAs; 0/RNA, Small Interfering; EC Proteins c-yes; EC protein, human; EC protein-tyrosine kinase; EC Kinases; EC Kinases; EC Protein Kinase 1; EC Protein Kinase 3; EC Proteins

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