title: The expression of tumor suppressor gene Cyld is upregulated by histone deacetylace inhibitors in human hepatocellular carcinoma cell lines.
abstract: CYLD is a deubiquitinating enzyme that exerts a tumor suppressive function. Its downregulation or inactivation has been associated with the development of several types of malignancies including hepatocellular carcinoma (HCC). HCC cells display significantly lower Cyld expression compared to primary human hepatocytes, and Cyld downregulation can contribute to apoptotic resistance of HCC cells. Little is known about the mechanism of Cyld downregulation in human HCC cells. In the present study we explored the possible regulation of Cyld expression by histone deacetylases (HDACs) in human HCC cell lines. We demonstrated that the HDAC inhibitors suberoylanilide hydroxamic acid, sodium butyrate, and trichostatin A induced the upregulation of both mRNA and protein levels of CYLD in two different HCC cell lines, HepG2 and Huh7. Our results demonstrate the involvement of HDACs in the downregulation of Cyld expression in HCC cells and support and may improve the use of HDAC inhibitors for the treatment for HCC.
authors: School of Biology, Aristotle University of Thessaloniki, Thessaloniki, Macedonia, Greece.
authors: Panorea
authors: P
authors: Kotantaki
authors: School of Biology, Aristotle University of Thessaloniki, Thessaloniki, Macedonia, Greece. gmosialo@bio.auth.gr.
authors: George
authors: G
authors: Mosialos
mesh_terms: D020148:Butyric Acid / Q000494:pharmacology; D006528:Carcinoma, Hepatocellular / Q000235:genetics*; D045744:Cell Line, Tumor; D000074749:Deubiquitinating Enzyme CYLD; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology*; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology; D008113:Liver Neoplasms / Q000235:genetics*; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects*; D000077337:Vorinostat
chemical_list: D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; D025521:Tumor Suppressor Proteins; D020148:Butyric Acid; C012589:trichostatin A; D000077337:Vorinostat; C409984:CYLD protein, human; D000074749:Deubiquitinating Enzyme CYLD
keywords: Cyld; HDAC; epigenetics; hepatocellular carcinoma; sodium butyrate; suberoylanilide hydroxamic acid; trichostatin A