title: MicroRNA-708 induces apoptosis and suppresses tumorigenicity in renal cancer cells.
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.
authors.affiliation: Department of Urology, Veterans Affairs Medical Center, San Francisco, California 94121, USA.
authors.forename: Sharanjot
authors.initials: S
authors.lastname: Saini
authors.forename: Soichiro
authors.initials: S
authors.lastname: Yamamura
authors.forename: Shahana
authors.initials: S
authors.lastname: Majid
authors.forename: Varahram
authors.initials: V
authors.lastname: Shahryari
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Hirata
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Tanaka
authors.forename: Rajvir
authors.initials: R
authors.lastname: Dahiya
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics*; D015820:Cadherins / Q000235:genetics / Q000378:metabolism; D002461:Cell Line, Transformed; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic; D015972:Gene Expression Regulation, Neoplastic; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000235:genetics; D007680:Kidney Neoplasms / Q000235:genetics / Q000473:pathology; D051379:Mice; D035683:MicroRNAs / Q000235:genetics*; D009361:Neoplasm Invasiveness / Q000235:genetics; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D000077022:Survivin; D000074165:Zinc Finger E-box Binding Homeobox 2
chemical_list: C107489:BIRC5 protein, human; D015820:Cadherins; D018398:Homeodomain Proteins; D051034:Inhibitor of Apoptosis Proteins; C568528:MIRN708 microRNA, human; D035683:MicroRNAs; D012097:Repressor Proteins; D000077022:Survivin; C492363:ZEB2 protein, human; D000074165:Zinc Finger E-box Binding Homeobox 2