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MicroRNA-205 Inhibits Src-Mediated Oncogenic Pathways in 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 
 CANCER RESEARCH, Vol.71(7) : 2611-2621, 2011 
Journal Title
Issue Date
Apoptosis/physiology ; Carcinoma, Renal Cell/enzymology ; Carcinoma, Renal Cell/genetics ; Carcinoma, Renal Cell/metabolism* ; Cell Cycle/physiology ; Cell Growth Processes/physiology ; Cell Line, Tumor ; Cell Movement/physiology ; Down-Regulation ; Humans ; Kidney Neoplasms/enzymology ; Kidney Neoplasms/genetics ; Kidney Neoplasms/metabolism* ; MAP Kinase Signaling System ; MicroRNAs/biosynthesis* ; MicroRNAs/genetics ; Mitogen-Activated Protein Kinase 1/metabolism ; Mitogen-Activated Protein Kinase 3/metabolism ; Proto-Oncogene Proteins c-yes/genetics ; RNA, Small Interfering/administration & dosage ; RNA, Small Interfering/genetics ; raf Kinases/metabolism ; ras Proteins/metabolism ; src-Family Kinases/antagonists & inhibitors* ; src-Family Kinases/genetics ; src-Family Kinases/metabolism
MicroRNA-205 ; Src ; Lyn ; Yes ; renal cancer
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.
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2. College of Dentistry (치과대학) > Dept. of Oral Biology (구강생물학교실) > 1. Journal Papers
Yonsei Authors
Chang, In Ik(장인익)
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