HIF1 regulates WSB‐1 expression to promote hypoxia‐induced chemoresistance in hepatocellular carcinoma cells. Issue 16 (19th June 2013) - Tong, Ying
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. Abstract : Hypoxia induces WSB‐1 expression in hepatocellular carcinoma cells. Hypoxia‐induced WSB‐1 expression is mediated by HIF‐1 transcription factor. Identification and validation of a functional HRE in the WSB‐1 promoter. WSB‐1 regulates the abundance of HIPK2 during hypoxia. Silencing the expression of WSB‐1 sensitizes hypoxic HCC cells to etoposide‐induced apoptosis.