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MicroRNA-708 Induces Apoptosis and Suppresses Tumorigenicity in Renal Cancer Cells.
- Source :
-
Cancer Research . Oct2011, Vol. 71 Issue 19, p6208-6219. 12p. - Publication Year :
- 2011
-
Abstract
- Cancer pathogenesis is restricted by stresses that compromise cell division and survival. In this study, we identify miR-708, a little studied member of a set of microRNAs that have been implicated in stress control, as an important tumor suppressor in renal cell carcinoma (RCC). miR-708 expression was attenuated widely in human RCC specimens. Restoration of miR-708 expression in RCC cell lines decreased cell growth, clonability, invasion, and migration and elicited a dramatic increase in apoptosis. Moreover, intratumoral delivery of miR-708 was sufficient to trigger in vivo regression of established tumors in murine xenograft models of human RCC. Investigation of the targets of miR-708 identified the inhibitor of apoptosis protein survivin as important. siRNA-mediated knockdown of survivin partially phenocopied miR-708 overexpression suggesting that the proapoptotic role of miR-708 may be mediated primarily through survivin regulation. Additionally, we identified the E-cadherin regulators ZEB2 and BMI1 as likely miR-708 targets. Taken together, our findings define a major tumor suppressive role for miR-708, which may offer an attractive new target for prognostic and therapeutic intervention in RCC. [ABSTRACT FROM AUTHOR]
- Subjects :
- *APOPTOSIS
*CARCINOGENESIS
*CELL division
*CANCER cells
*RENAL cell carcinoma
Subjects
Details
- Language :
- English
- ISSN :
- 00085472
- Volume :
- 71
- Issue :
- 19
- Database :
- Academic Search Index
- Journal :
- Cancer Research
- Publication Type :
- Academic Journal
- Accession number :
- 66752215
- Full Text :
- https://doi.org/10.1158/0008-5472.CAN-11-0073