HJURP Promotes Malignant Progression and Mediates Sensitivity to Cisplatin and WEE1-inhibitor in Serous Ovarian Cancer.
HJURP Promotes Malignant Progression and Mediates Sensitivity to Cisplatin and WEE1-inhibitor in Serous Ovarian Cancer.
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HJURP 促进浆液性卵巢癌的恶性进展并调节对顺铂和 WEE1 抑制剂的敏感性
DOI：
10.7150/ijbs.65589
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发表时间：
2022
影响因子：
9.2
通讯作者：
Kong B
中科院分区：
文献类型：
--
作者：
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
卵巢癌是最致命的妇科恶性肿瘤。复发和化疗耐药是导致预后不良的严峻挑战。 HJURP 是 CENP-A 的分子伴侣，与多种肿瘤的侵袭性进展相关。然而，HJURP 在卵巢癌中的功能尚未阐明。在我们的研究中，我们发现 HJURP 在卵巢癌中过度表达，并且 HJURP 的高表达与不良预后相关。 HJURP敲低可以抑制卵巢癌细胞的增殖、转移并诱导G0/G1期停滞。此外，下一代测序（NGS）揭示了WEE1通过沉默HJURP而下调。进一步的机制研究表明HJURP通过MYC调节WEE1，荧光素酶分析表明MYC是WEE1的转录因子。此外，我们研究了沉默 HJURP 通过 MYC/WEE1 轴增加了卵巢癌细胞对顺铂的敏感性，并且 HJURP 参与了顺铂引起的损伤的 DNA 修复。更有趣的是，沉默HJURP可以增强卵巢癌细胞对AZD1775的敏感性，提高顺铂联合AZD1775联合治疗的协同效应。总的来说，我们的数据显示HJURP促进卵巢癌的肿瘤进展和化疗耐药，并且HJURP有潜力成为顺铂和AZD1775联合治疗卵巢癌的新治疗靶点。
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.
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影响因子：
4
作者：
Hu B;Wang Q;Wang Y;Chen J;Li P;Han M
通讯作者：
Han M
RECQL4，受 miR-10a-5p 负调控，通过 MAFB 促进卵巢癌细胞增殖和侵袭
影响因子：
4.7
作者：
Guo L;Li Y;Zhao C;Peng J;Song K;Chen L;Zhang P;Ma H;Yuan C;Yan S;Fang Y;Kong B
通讯作者：
Kong B
影响因子：
16.6
作者：
Labidi-Galy SI;Papp E;Hallberg D;Niknafs N;Adleff V;Noe M;Bhattacharya R;Novak M;Jones S;Phallen J;Hruban CA;Hirsch MS;Lin DI;Schwartz L;Maire CL;Tille JC;Bowden M;Ayhan A;Wood LD;Scharpf RB;Kurman R;Wang TL;Shih IM;Karchin R;Drapkin R;Velculescu VE
通讯作者：
Velculescu VE
DOI：
10.1158/1078-0432.ccr-20-3089
发表时间：
2021-02-15
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Keenan TE;Li T;Vallius T;Guerriero JL;Tayob N;Kochupurakkal B;Davis J;Pastorello R;Tahara RK;Anderson L;Conway J;He MX;Shannon E;Godin RE;Sorger PK;D'Andrea A;Overmoyer B;Winer EP;Mittendorf EA;Van Allen EM;Shapiro GI;Tolaney SM
通讯作者：
Tolaney SM
影响因子：
28.2
作者：
Aarts, Marieke;Sharpe, Rachel;Turner, Nicholas C.
通讯作者：
Turner, Nicholas C.