HJURP inhibits proliferation of ovarian cancer cells by regulating CENP-A/CENP-N

Bull Cancer. 2022 Oct;109(10):1007-1016. doi: 10.1016/j.bulcan.2021.12.011. Epub 2022 Aug 6.

Abstract

Objective: High expression of Holliday Junction-Recognizing Protein (HJURP) has been shown to be a marker of poor prognosis in ovarian cancer. The objective of this study was to investigate the molecular mechanisms of HJURP in ovarian cancer (OC) progression.

Procedures: Gene Expression Profiling Interactive Analysis (GEPIA) was used to analyze the gene expression profile. Real-time quantitative PCR (qRT-PCR) was used to detect the expression level and correlation of HJURP and centromere protein-A (CENP-A) in OC tissues and cell lines. CCK-8 assay was used to detect cell proliferation. The expression level of apoptosis-related proteins and cell cycle-related proteins were detected by western blotting. Cell cycle and mitochondrial content were determined by flow cytometry.

Results: The results showed that HJURP was up-regulated in OC tissues and cell lines, while the cell proliferation was inhibited after transfecting by si-HJURP. Knockdown of HJURP promoted cell apoptosis. Meanwhile, low-expression of HJURP could down-regulate cell replication cycle-related proteins (Cyclin-dependent kinase 2, cyclinD1 and Cyclin-dependent kinase 4) and make cell replication stay in the S phase. Moreover, further studies showed that HJURP was positively correlated with CENP-A in OC tissues. Finally, the rescue experiment further verified that HJURP targeted regulation of CENP-A in OC.

Conclusions: The study indicated that HJURP plays a significant role in OC and could target CENP-A to regulate OC cell growth. These findings provide a clue to the diagnosis and treatment of OC.

Keywords: CENP-N; HJURP; Ovarian cancer.

MeSH terms

  • Cell Line, Tumor
  • Cell Proliferation
  • Centromere Protein A* / genetics
  • Centromere Protein A* / metabolism
  • Centromere* / metabolism
  • Chromosomal Proteins, Non-Histone* / genetics
  • Chromosomal Proteins, Non-Histone* / metabolism
  • Cyclin-Dependent Kinase 2 / genetics
  • Cyclin-Dependent Kinase 2 / metabolism
  • Cyclin-Dependent Kinase 4 / genetics
  • Cyclin-Dependent Kinase 4 / metabolism
  • DNA, Cruciform
  • DNA-Binding Proteins* / genetics
  • DNA-Binding Proteins* / metabolism
  • Female
  • Humans
  • Ovarian Neoplasms* / genetics

Substances

  • CENPA protein, human
  • CENPN protein, human
  • Centromere Protein A
  • Chromosomal Proteins, Non-Histone
  • DNA, Cruciform
  • DNA-Binding Proteins
  • HJURP protein, human
  • Cyclin-Dependent Kinase 2
  • Cyclin-Dependent Kinase 4