MicroRNA-708 induces apoptosis and suppresses tumorigenicity in renal cancer cells

Sharanjot Saini, Soichiro Yamamura, Shahana Majid, Varahram Shahryari, Hiroshi Hirata, Yuichiro Tanaka, Rajvir Dahiya

Research output: Contribution to journalArticlepeer-review

112 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)6208-6219
Number of pages12
JournalCancer Research
Volume71
Issue number19
DOIs
StatePublished - Oct 1 2011

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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