Hypomethylation-driven overexpression of HJURP promotes progression of hepatocellular carcinoma and is associated with poor prognosis

• Published in: Biochemical and biophysical research communications Vol. 566; pp. 67 - 74
• Main Authors: Li, Ye, Yi, Qing, Liao, Xiaoli, Han, Chenglong, Zheng, Li, Li, Hui, Yu, Qian, Yan, Xuexin, Chen, Xinyu, Zhu, Huawei, Zhao, Bi, Lin, Qiulu, Liang, Li, Wang, Li, Qin, Fanghui, Xie, Weimin, Li, Yongqiang, Huang, Wenfeng
• Format: Journal Article
• Language: English
• Published: Elsevier Inc 20.08.2021
• Subjects: Centromere maintenance; Hepatocellular carcinoma; HJURP; Prognosis; Tumor progression; HJURP; Hepatocellular carcinoma; Centromere maintenance; Prognosis; Tumor progression
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2021.05.102

Our previous studies have initially identified HJURP, which encodes a Holliday junction recognizing protein, as a hepatocellular carcinoma (HCC) susceptibility gene. In this report, we showed that the HJURP is highly expressed in HCC tissues compared to adjacent normal tissues. Overexpression of HJURP in HCC tissues is mainly due to the hypomethylation of HJURP promoter region. Clinically, high expression of HJURP is significantly associated with poor overall survival and disease-free survival of patients with HCC, as well as in multiple other types of cancer. Gain- and loss-of functional studies demonstrated that HJURP promotes HCC cell proliferation, clone formation, migration and invasion. Additionally, HJURP enhances HCC tumorigenesis via reducing G0/G1 arrest and apoptosis. Mechanistically, by gene set enrichment analysis (GSEA) analysis, HJURP was identified as a modulator involved in CENPA-mediated centromere maintenance. Our results provide evidence of HJURP as an important oncogene that promotes HCC progression, and the HJURP pathway may be a potential target for the treatment of HCC. •HJURP is overexpressed in HCC and many other types of cancer, which is mainly driven by DNA hypomethylation.•Overexpression of HJURP is significantly associated with poor outcomes of patients with HCC.•HJURP functions as an oncogene in HCC cells via promoting cell growth, migration and invasion.•Integrated genomic analysis indicates the involvement of HJURP in CENPA-mediated centromere maintenance.