MicroRNA-708 Induces Apoptosis and Suppresses Tumorigenicity in Renal Cancer Cells

University of California, San Francisco, San Francisco, California, United States
Cancer Research (Impact Factor: 9.33). 08/2011; 71(19):6208-19. DOI: 10.1158/0008-5472.CAN-11-0073
Source: PubMed


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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    • "MicroRNAs (miRNAs) are a class of highly conserved short RNAs that regulate diverse cellular processes by binding to the 3′untranslated region (3′UTR) of target messenger RNAs (mRNAs) [3,4]. Increasing numbers of studies have suggested that miRNAs play an important role in HCC development, such as apoptosis [5,6], proliferation [7,8], autophagy [9], EMT. [10]. "
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    • "Tumorigenicity in nude mice was determined as described previously [23,38]. To evaluate the chemosensitivity effect of miR-34a, four groups of 6 mice each were injected subcutaneously with T24 cells at a single site. "
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