Journal
FEBS LETTERS
Volume 587, Issue 16, Pages 2530-2535Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.febslet.2013.06.017
Keywords
Hypoxia; HIF-1; WSB-1; HIPK2; Chemoresistance
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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-1 alpha in HCC cells by RNA interference abolishes hypoxia-induced WSB-1 expression. Using chromatin immunoprecipitation and luciferase reporter assays, we identified a HIRE 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. (C) 2013 Published by Elsevier B.V. on behalf of the Federation of European Biochemical Societies.
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