title: HIF1 regulates WSB-1 expression to promote hypoxia-induced chemoresistance in hepatocellular carcinoma cells.
abstract: WSB-1 is involved in DNA damage response by targeting homeodomain-interacting protein kinase 2 (HIPK2) for ubiquitination and degradation. Here, we report that hypoxia significantly up-regulates the expression of WSB-1 in human hepatocellular carcinoma (HCC) cells. We also provide evidence that WSB-1 is a target of hypoxia-inducible factor 1 (HIF-1). Silencing the expression of HIF-1α in HCC cells by RNA interference abolishes hypoxia-induced WSB-1 expression. Using chromatin immunoprecipitation and luciferase reporter assays, we identified a HRE of the WSB-1 gene. Moreover, silencing the expression of WSB-1 by RNA interference rescues HIPK2 expression in hypoxic HCC cells and promotes etoposide-induced cell death in hypoxic HCC cells. Taken together, these data shed light on the mechanisms underlying hypoxia-induced chemoresistance in HCC cells.
authors.affiliation: Department of Liver Surgery, Renji Hospital, Medical College of Shanghai Jiaotong University, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Tong
authors.forename: Qi-Gen
authors.initials: QG
authors.lastname: Li
authors.forename: Tian-Yu
authors.initials: TY
authors.lastname: Xing
authors.forename: Ming
authors.initials: M
authors.lastname: Zhang
authors.forename: Jian-Jun
authors.initials: JJ
authors.lastname: Zhang
authors.forename: Qiang
authors.initials: Q
authors.lastname: Xia
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D017209:Apoptosis; D006528:Carcinoma, Hepatocellular / Q000201:enzymology*; D002352:Carrier Proteins / Q000378:metabolism; D015687:Cell Hypoxia; D004249:DNA Damage; D019008:Drug Resistance, Neoplasm; D005047:Etoposide / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic; D056945:Hep G2 Cells; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism*; D047908:Intracellular Signaling Peptides and Proteins; D008113:Liver Neoplasms / Q000201:enzymology*; D011401:Promoter Regions, Genetic; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D011506:Proteins / Q000378:metabolism*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D013778:Tetrazolium Salts / Q000494:pharmacology; D013844:Thiazoles / Q000494:pharmacology
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D002352:Carrier Proteins; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D047908:Intracellular Signaling Peptides and Proteins; D011506:Proteins; D034741:RNA, Small Interfering; D013778:Tetrazolium Salts; D013844:Thiazoles; C120287:WSB1 protein, human; D005047:Etoposide; C115114:HIPK2 protein, human; D017346:Protein Serine-Threonine Kinases; C022616:thiazolyl blue
keywords: Chemoresistance; HIF-1; HIPK2; Hypoxia; WSB-1