title: Hypoxia-inducible factor-1alpha suppressed hepatocellular carcinoma cell apoptosis through influencing on Omi/HtrA2 expression and its releasing from the mitochondrion.
abstract: Hypoxia-inducible factor-1alpha (HIF-1alpha) plays an important role in regulating hepatoma cell apoptosis. However, conclusions of different studies about the effects of HIF-1alpha expression on hepatoma cell apoptosis remain controversial. Omi/HtrA2 promotes cell apoptosis in some human cancer cells. Our previous experiments have demonstrated that primary hepatocellular carcinoma may need Omi/HtrA2 expression for cell apoptosis. Thus, we investigated the effect of HIF-1alpha on hepatocellular carcinoma cell apoptosis and Omi/ HtrA2 expression. In our study we found that HIF-1alpha gene could suppress hepatoma cell apoptosis, and Omi/HtrA2 mRNA and protein expression decreased with HIF-1alpha expression increase while Bcl-2 mRNA and protein expression increased with HIF-1alpha expression increase in HepG2 cells under normoxia condition. Meanwhile, Omi/HtrA2 protein expression increased with HIF-1alpha expression decrease in HepG2 cells under hypoxia culture. Taken together, these results demonstrated that HIF-1alpha suppressed hepatocellular carcinoma cell apoptosis through inhibiting Omi/HtrA2 expression and upregulating Bcl-2 expression to impede Omi/ HtrA2 releasing from the mitochondrion. The present finding further enriched and supported the role of HIF-1alpha expression on cell apoptosis of hepatoma cells.
authors.affiliation: Hepatobiliary Surgery Qilu Hospital, ShanDong University, Jinan, China.
authors.forename: Zongquan
authors.initials: Z
authors.lastname: Xu
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Chen
authors.forename: Cheng
authors.initials: C
authors.lastname: Peng
authors.forename: Enyu
authors.initials: E
authors.lastname: Liu
authors.forename: Yunguang
authors.initials: Y
authors.lastname: Li
authors.forename: Changhai
authors.initials: C
authors.lastname: Li
authors.forename: Jun
authors.initials: J
authors.lastname: Niu
mesh_terms: D017209:Apoptosis; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D015687:Cell Hypoxia; D015972:Gene Expression Regulation, Neoplastic; D056945:Hep G2 Cells; D000074923:High-Temperature Requirement A Serine Peptidase 2; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics / Q000378:metabolism*; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D008928:Mitochondria / Q000235:genetics; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D012697:Serine Endopeptidases / Q000235:genetics / Q000378:metabolism*
chemical_list: C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D024101:Mitochondrial Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D012697:Serine Endopeptidases; C000615914:HTRA2 protein, human; D000074923:High-Temperature Requirement A Serine Peptidase 2