Chromatin-associated OGT promotes the malignant progression of hepatocellular carcinoma by activating ZNF263

Wang, Lingyan1; Li, Guofang1; Zhou, Ziyu1; Ge, Chang1; Chen, Qiushi2,3; Liu, Yajie1; Zhang, Nana1; Zhang, Keren4; Niu, Mingshan5; Li, Wenli1; Zhong, Xiaomin6; Wu, Sijin7; Zhang, Jianing1; Liu, Yubo1

2023-06-01

10.1038/s41388-023-02751-1

ONCOGENE   影响因子和分区

0950-9232

1476-5594

Reversible and dynamic O-GlcNAcylation regulates vast networks of highly coordinated cellular and nuclear processes. Although dysregulation of the sole enzyme O-GlcNAc transferase (OGT) was shown to be associated with the progression of hepatocellular carcinoma (HCC), the mechanisms by which OGT controls the cis-regulatory elements in the genome and performs transcriptional functions remain unclear. Here, we demonstrate that elevated OGT levels enhance HCC proliferation and metastasis, in vitro and in vivo, by orchestrating the transcription of numerous regulators of malignancy. Diverse transcriptional regulators are recruited by OGT in HCC cells undergoing malignant progression, which shapes genome-wide OGT chromatin cis-element occupation. Furthermore, an unrecognized cooperation between ZNF263 and OGT is crucial for activating downstream transcription in HCC cells. We reveal that O-GlcNAcylation of Ser662 is responsible for the chromatin association of ZNF263 at candidate gene promoters and the OGT-facilitated HCC malignant phenotypes. Our data establish the importance of aberrant OGT activity and ZNF263 O-GlcNAcylation in the malignant progression of HCC and support the investigation of OGT as a therapeutic target for HCC.

SCI

英语

其他

National Natural Science Foundation of China[32171282] ; Fundamental Research Funds for the Central Universities[DUT22YG131]

Biochemistry & Molecular Biology ; Oncology ; Cell Biology ; Genetics & Heredity

Biochemistry & Molecular Biology ; Oncology ; Cell Biology ; Genetics & Heredity

WOS:001019409400002

SPRINGERNATURE

MOLECULAR BIOLOGY & GENETICS

Web of Science

1.Dalian Univ Technol, Sch Life & Pharmaceut Sci, Panjin, Peoples R China
2.Univ Hong Kong, Dept Chem, Hong Kong, Peoples R China
3.Lab Synthet Chem & Chem Biol Ltd, Hong Kong, Peoples R China
4.Southern Univ Sci & Technol, Coll Sci, Dept Chem, Shenzhen, Peoples R China
5.Xuzhou Med Univ, Blood Dis Inst, Xuzhou, Jiangsu, Peoples R China
6.Nanjing Med Univ, Affiliated Huaian 1 Peoples Hosp, Dept Oncol, Huaian, Peoples R China
7.Shenzhen Jingtai Technol Co Ltd XtalPi, Shenzhen, Peoples R China

Wang, Lingyan,Li, Guofang,Zhou, Ziyu,et al. Chromatin-associated OGT promotes the malignant progression of hepatocellular carcinoma by activating ZNF263[J]. ONCOGENE,2023,42(30).

Wang, Lingyan.,Li, Guofang.,Zhou, Ziyu.,Ge, Chang.,Chen, Qiushi.,...&Liu, Yubo.(2023).Chromatin-associated OGT promotes the malignant progression of hepatocellular carcinoma by activating ZNF263.ONCOGENE,42(30).

Wang, Lingyan,et al."Chromatin-associated OGT promotes the malignant progression of hepatocellular carcinoma by activating ZNF263".ONCOGENE 42.30(2023).