Zhang Yuyang, Zhang Wei, Sun Lili, Yue Yuanyuan, Shen Dan, Tian Bingbing, Du Meng, Dong Meicen, Liu Yang, Zhang Dan
The Second Department of Oncology, General Hospital,Fushun Mining Bureau, Liaoning Health Industry Group, 113008 Fushun, Liaoning Province, China.
Department of Pathology, General Hospital, Fushun Mining Bureau, Liaoning Health Industry Group, 113008 Fushun, Liaoning Province, China.
Bull Cancer. 2022 Oct;109(10):1007-1016. doi: 10.1016/j.bulcan.2021.12.011. Epub 2022 Aug 6.
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.
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.
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.
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.
研究表明，霍利迪连接点识别蛋白（HJURP）的高表达是卵巢癌预后不良的一个标志物。本研究的目的是探讨HJURP在卵巢癌（OC）进展中的分子机制。
利用基因表达谱交互式分析（GEPIA）分析基因表达谱。采用实时定量聚合酶链反应（qRT-PCR）检测OC组织和细胞系中HJURP和着丝粒蛋白A（CENP-A）的表达水平及相关性。采用CCK-8法检测细胞增殖情况。通过蛋白质免疫印迹法检测凋亡相关蛋白和细胞周期相关蛋白的表达水平。通过流式细胞术检测细胞周期和线粒体含量。
结果显示，HJURP在OC组织和细胞系中表达上调，而转染si-HJURP后细胞增殖受到抑制。敲低HJURP可促进细胞凋亡。同时，HJURP低表达可下调细胞复制周期相关蛋白（细胞周期蛋白依赖性激酶2、细胞周期蛋白D1和细胞周期蛋白依赖性激酶4），使细胞复制停滞于S期。此外，进一步研究表明，OC组织中HJURP与CENP-A呈正相关。最后，挽救实验进一步证实HJURP在OC中靶向调控CENP-A。
本研究表明，HJURP在OC中发挥重要作用，可靶向CENP-A调控OC细胞生长。这些发现为OC的诊断和治疗提供了线索。
