title: O-GlcNAcylation of histone deacetylases 1 in hepatocellular carcinoma promotes cancer progression.
abstract: Hepatocellular carcinoma (HCC) is a malignant tumor originating in the liver. Previous studies have indicated that O-GlcNAc transferase (OGT) and histone deacetylase-1 (HDAC1) play important roles in the pathogenesis of HCC. In the present study, we investigated the physical link between OGT and HDAC1. The O-GlcNAcylation of HDAC1 is overexpressed in HCC. We found that HDAC1 has two major sites of O-GlcNAcylation in its histone deacetylase domain. HDAC1 O-GlcNAcylation increases the activated phosphorylation of HDAC1, which enhances its enzyme activity. HDAC1 O-GlcNAc mutants promote the p21 transcription regulation through affecting the acetylation levels of histones from chromosome, and then influence the proliferation of HCC cells. We also found that mutants of O-GlcNAcylation site of HDAC1 affect invasion and migration of HepG2 cells. E-cadherin level is highly up-regulated in HDAC1 O-GlcNAc mutant-treated liver cancer cells, which inhibit the occurrence and development of HCC. Our findings suggest that OGT promotes the O-GlcNAc modification of HDAC1in the development of HCC. Therefore, inhibiting O-GlcNAcylation of HDAC1 may repress the progression of HCC.
authors.affiliation: The Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Nantong University, 19 Qixiu Road, Nantong, 226001 Jiangsu, People's Republic of China.
authors.forename: Guizhou
authors.initials: G
authors.lastname: Zhu
authors.affiliation: The Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Nantong University, 19 Qixiu Road, Nantong, 226001 Jiangsu, People's Republic of China.
authors.forename: Tao
authors.initials: T
authors.lastname: Tao
authors.affiliation: The Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Nantong University, 19 Qixiu Road, Nantong, 226001 Jiangsu, People's Republic of China.
authors.forename: Dongmei
authors.initials: D
authors.lastname: Zhang
authors.affiliation: The Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Nantong University, 19 Qixiu Road, Nantong, 226001 Jiangsu, People's Republic of China.
authors.forename: Xiaojuan
authors.initials: X
authors.lastname: Liu
authors.affiliation: The Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Nantong University, 19 Qixiu Road, Nantong, 226001 Jiangsu, People's Republic of China.
authors.forename: Huiyuan
authors.initials: H
authors.lastname: Qiu
authors.affiliation: The Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Nantong University, 19 Qixiu Road, Nantong, 226001 Jiangsu, People's Republic of China.
authors.forename: LiJian
authors.initials: L
authors.lastname: Han
authors.affiliation: The Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Nantong University, 19 Qixiu Road, Nantong, 226001 Jiangsu, People's Republic of China.
authors.forename: Zhiwei
authors.initials: Z
authors.lastname: Xu
authors.affiliation: The Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Nantong University, 19 Qixiu Road, Nantong, 226001 Jiangsu, People's Republic of China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Xiao
authors.affiliation: The Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Nantong University, 19 Qixiu Road, Nantong, 226001 Jiangsu, People's Republic of China.
authors.forename: Chun
authors.initials: C
authors.lastname: Cheng
authors.affiliation: The Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Nantong University, 19 Qixiu Road, Nantong, 226001 Jiangsu, People's Republic of China.|Department of Co-innovation Center of Neuroregeneration, Nantong University, 19 Qixiu Road, Nantong, 226001 Jiangsu, People's Republic of China.
authors.forename: Aiguo
authors.initials: A
authors.lastname: Shen
mesh_terms: D000215:Acylation; D015703:Antigens, CD; D015820:Cadherins / Q000235:genetics / Q000378:metabolism; D006528:Carcinoma, Hepatocellular / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D002465:Cell Movement; D049109:Cell Proliferation; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics / Q000378:metabolism; D018450:Disease Progression; D015972:Gene Expression Regulation, Neoplastic; D057809:HEK293 Cells; D056945:Hep G2 Cells; D056284:Histone Deacetylase 1 / Q000235:genetics* / Q000378:metabolism; D006657:Histones / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008113:Liver Neoplasms / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D017351:N-Acetylglucosaminyltransferases / Q000235:genetics* / Q000378:metabolism; D011499:Protein Processing, Post-Translational
chemical_list: D015703:Antigens, CD; C513384:CDH1 protein, human; D015820:Cadherins; D050759:Cyclin-Dependent Kinase Inhibitor p21; D006657:Histones; D017351:N-Acetylglucosaminyltransferases; C449880:O-GlcNAc transferase; C110550:HDAC1 protein, human; D056284:Histone Deacetylase 1
keywords: O-GlcNAc transferase; O-GlcNAcylation; cell proliferation; hepatocellular carcinoma; histone deacetylase-1