TY - JOUR
T1 - MicroRNA-708 induces apoptosis and suppresses tumorigenicity in renal cancer cells
AU - Saini, Sharanjot
AU - Yamamura, Soichiro
AU - Majid, Shahana
AU - Shahryari, Varahram
AU - Hirata, Hiroshi
AU - Tanaka, Yuichiro
AU - Dahiya, Rajvir
PY - 2011/10/1
Y1 - 2011/10/1
N2 - 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.
AB - 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.
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UR - http://www.scopus.com/inward/citedby.url?scp=80053377344&partnerID=8YFLogxK
U2 - 10.1158/0008-5472.CAN-11-0073
DO - 10.1158/0008-5472.CAN-11-0073
M3 - Article
C2 - 21852381
AN - SCOPUS:80053377344
SN - 0008-5472
VL - 71
SP - 6208
EP - 6219
JO - Cancer Research
JF - Cancer Research
IS - 19
ER -