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

Research output: Contribution to journalArticle

Abstract

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 30-UTR (untranslated region) sequences complementary to either Src, Lyn, or Yes, which was abolished by mutations in these 30-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.

Original languageEnglish (US)
Pages (from-to)2611-2621
Number of pages11
JournalCancer Research
Volume71
Issue number7
DOIs
StatePublished - Apr 1 2011
Externally publishedYes

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Kidney Neoplasms
MicroRNAs
Untranslated Regions
Renal Cell Carcinoma
Cell Movement
G1 Phase Cell Cycle Checkpoints
Focal Adhesion Protein-Tyrosine Kinases
Neoplasms
src-Family Kinases
Cell Shape
MAP Kinase Signaling System
Cyclin D1
Tumor Cell Line
Luciferases
Protein Kinases
Cell Differentiation
Cell Survival
Plasmids
Cell Proliferation
Apoptosis

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Majid, S., Saini, S., Dar, A. A., Hirata, H., Shahryari, V., Tanaka, Y., ... Dahiya, R. (2011). MicroRNA-205 inhibits Src-mediated oncogenic pathways in renal cancer. Cancer Research, 71(7), 2611-2621. https://doi.org/10.1158/0008-5472.CAN-10-3666

MicroRNA-205 inhibits Src-mediated oncogenic pathways in renal cancer. / Majid, Shahana; Saini, Sharanjot; Dar, Altaf A.; Hirata, Hiroshi; Shahryari, Varahram; Tanaka, Yuichiro; Yamamura, Soichiro; Ueno, Koji; Zaman, Mohd Saif; Singh, Kamaldeep; Chang, Inik; Deng, Guoren; Dahiya, Rajvir.

In: Cancer Research, Vol. 71, No. 7, 01.04.2011, p. 2611-2621.

Research output: Contribution to journalArticle

Majid, S, Saini, S, Dar, AA, Hirata, H, Shahryari, V, Tanaka, Y, Yamamura, S, Ueno, K, Zaman, MS, Singh, K, Chang, I, Deng, G & Dahiya, R 2011, 'MicroRNA-205 inhibits Src-mediated oncogenic pathways in renal cancer', Cancer Research, vol. 71, no. 7, pp. 2611-2621. https://doi.org/10.1158/0008-5472.CAN-10-3666
Majid S, Saini S, Dar AA, Hirata H, Shahryari V, Tanaka Y et al. MicroRNA-205 inhibits Src-mediated oncogenic pathways in renal cancer. Cancer Research. 2011 Apr 1;71(7):2611-2621. https://doi.org/10.1158/0008-5472.CAN-10-3666
Majid, Shahana ; Saini, Sharanjot ; Dar, Altaf A. ; Hirata, Hiroshi ; Shahryari, Varahram ; Tanaka, Yuichiro ; Yamamura, Soichiro ; Ueno, Koji ; Zaman, Mohd Saif ; Singh, Kamaldeep ; Chang, Inik ; Deng, Guoren ; Dahiya, Rajvir. / MicroRNA-205 inhibits Src-mediated oncogenic pathways in renal cancer. In: Cancer Research. 2011 ; Vol. 71, No. 7. pp. 2611-2621.
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