Int J Biol Sci 2022; 18(3):1188-1210. doi:10.7150/ijbs.65589 This issue

Research Paper

HJURP Promotes Malignant Progression and Mediates Sensitivity to Cisplatin and WEE1-inhibitor in Serous Ovarian Cancer

Zhiyuan Dou1,2, Chunping Qiu1, Xun Zhang1, Shu Yao1,2, Chen Zhao1,2, Zixiang Wang1,2, Ran Chu1,2, Jingying Chen1,2, Zhongshao Chen1, Rongrong Li1,2, Kun Wang1,2, Penglin Liu1, Chang Liu1,2, Kun Song1,2✉, Beihua Kong1,2✉

1. Department of Obstetrics and Gynecology, Qilu Hospital of Shandong University, Jinan, P.R. China.
2. Gynecologic Oncology key Laboratory, Qilu Hospital of Shandong University, Jinan, P.R. China.

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Citation:
Dou Z, Qiu C, Zhang X, Yao S, Zhao C, Wang Z, Chu R, Chen J, Chen Z, Li R, Wang K, Liu P, Liu C, Song K, Kong B. HJURP Promotes Malignant Progression and Mediates Sensitivity to Cisplatin and WEE1-inhibitor in Serous Ovarian Cancer. Int J Biol Sci 2022; 18(3):1188-1210. doi:10.7150/ijbs.65589. Available from https://www.ijbs.com/v18p1188.htm

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Abstract

Graphic abstract

Ovarian cancer is the most lethal gynecological malignancy. Recurrence and chemoresistance are tough challenges leading to poor prognosis. HJURP is a molecular chaperone of CENP-A, which is associated with aggressive progression in multiple tumors. However, the function of HJURP in ovarian cancer has not been elucidated. In our study, we found HJURP was over-expressed in ovarian cancer and high expression of HJURP was correlated to unfavorable prognosis. HJURP knockdown could inhibit proliferation, metastasis and induce G0/G1 stagnation of ovarian cancer cells. Besides, next-generation sequencing (NGS) unveiled that WEE1 was down-regulated by silencing HJURP. Further mechanistic research revealed that HJURP regulated WEE1 through MYC, and luciferase assay indicated that MYC was a transcription factor of WEE1. Additionally, we investigated that silencing HJURP increased sensitivity of ovarian cancer cells to cisplatin via MYC/WEE1 axis, and HJURP participated in DNA repair of cisplatin-induced damage. More interestingly, silencing HJURP could enhance sensitivity of ovarian cancer cells to AZD1775 and improve the synergistic effect of cisplatin plus AZD1775 combined therapy. Collectively, our data displays that HJURP promotes tumor progression and chemoresistance of ovarian cancer, and HJURP has potential to be a novel therapeutic target in the combined treatment with cisplatin and AZD1775 in ovarian cancer.

Keywords: HJURP, WEE1, AZD1775, chemoresistance, DNA damage repair