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- Title
O-GlcNAcylation of histone deacetylase-1 in hepatocellular carcinoma promotes cancer progression.
- Authors
Guizhou Zhu; Tao Tao; Dongmei Zhang; Xiaojuan Liu; Huiyuan Qiu; LiJian Han; Zhiwei Xu; Ying Xiao; Chun Cheng; Aiguo Shen
- 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.
- Subjects
HISTONE deacetylase; LIVER cancer; CANCER invasiveness; CARCINOGENESIS; GENETIC overexpression; PHOSPHORYLATION; CELL proliferation
- Publication
Glycobiology, 2016, Vol 26, Issue 8, p820
- ISSN
0959-6658
- Publication type
Article
- DOI
10.1093/glycob/cww025