title: Silencing of hypoxia inducible factor-1α by RNA interference inhibits growth of SK-NEP-1 Wilms tumour cells in vitro, and suppresses tumourigenesis and angiogenesis in vivo.
abstract: Wilms tumour is the most common tumour of the pediatric kidney. Elevation of hypoxia-inducible factor 1α (HIF-1α) has been detected in 93% to 100% of human Wilms tumour specimens, suggesting a potential value of HIF-1α as a therapeutic target for Wilms tumour. In the present study, a stable HIF-1α-silenced Wilms tumour cell strain was established by introducing HIF-1α short-hairpin RNA (shRNA) into SK-NEP-1 cells. Silencing of HIF-1α significantly reduced single-cell growth capacity, suppressed proliferation and arrested cell cycle of SK-NEP-1 cells. In addition, reduction of HIF-1α expression induced apoptosis in SK-NEP-1 cells, which was accompanied by increased levels of cleaved caspase-3, cleaved poly (ADP-ribose) polymerase (PARP) and Bax as well as downregulation of Bcl-2 in the cells. Furthermore, when inoculated subcutaneously in nude mice, HIF-1α-silenced SK-NEP-1 cells displayed retarded tumour growth and impaired tumour angiogenesis. In summary, the findings of this study suggest that HIF-1α plays a critical role in the development of Wilms tumour, and it may serve as a candidate target of gene therapy for Wilms tumour.
authors.affiliation: Department of Ultrasound Medicine, Shengjing Hospital of China Medical University, Shenyang, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Shi
authors.affiliation: Department of Ultrasound Medicine, Shengjing Hospital of China Medical University, Shenyang, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Paediatric Nephrology, Shengjing Hospital of China Medical University, Shenyang, China.
authors.forename: Xiuli
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Paediatric Urology, Shengjing Hospital of China Medical University, Shenyang, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Department of Pathology, Shengjing Hospital of China Medical University, Shenyang, China.
authors.forename: Dan
authors.initials: D
authors.lastname: Li
authors.affiliation: Department of Paediatric Urology, Shengjing Hospital of China Medical University, Shenyang, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Pathology, Shengjing Hospital of China Medical University, Shenyang, China.
authors.forename: Xianghong
authors.initials: X
authors.lastname: Yang
mesh_terms: D000818:Animals; D063646:Carcinogenesis / Q000235:genetics / Q000473:pathology*; D049108:Cell Enlargement; D045744:Cell Line, Tumor; D005260:Female; D020868:Gene Silencing; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000037:antagonists & inhibitors / Q000172:deficiency* / Q000235:genetics; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009389:Neovascularization, Pathologic / Q000235:genetics / Q000473:pathology* / Q000517:prevention & control; D034622:RNA Interference / Q000502:physiology*; D009396:Wilms Tumor / Q000235:genetics / Q000473:pathology* / Q000517:prevention & control
chemical_list: D051795:Hypoxia-Inducible Factor 1, alpha Subunit
keywords: RNA interference; Wilms tumour; angiogenesis; hypoxia-inducible factor 1α; tumourigenesis