Splicing Factor DDX23, Transcriptionally Activated by E2F1, Promotes Ovarian Cancer Progression by Regulating FOXM1.
Splicing Factor DDX23, Transcriptionally Activated by E2F1, Promotes Ovarian Cancer Progression by Regulating FOXM1.
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由 E2F1 转录激活的剪接因子 DDX23 通过调节 FOXM1 促进卵巢癌进展
DOI：
10.3389/fonc.2021.749144
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发表时间：
2021
影响因子：
4.7
通讯作者：
Kong B
中科院分区：
文献类型：
--
作者：
Zhao C;Li Y;Qiu C;Chen J;Wu H;Wang Q;Ma X;Song K;Kong B
卵巢癌仍然是最致命的妇科肿瘤。剪接因子的异常表达与肿瘤的发生发展密切相关。DEAD-box RNA解旋酶是剪接因子家族的重要成员。然而，它们在卵巢癌发生和发展中的作用尚不清楚。在本研究中，我们利用生物信息学方法鉴定了DEAD-box解旋酶23 （DDX23）是卵巢癌中一个关键的DEAD-box RNA解旋酶。我们发现DDX23在卵巢癌中表达上调，其高表达预示着不良预后。功能分析表明，DDX23沉默显著抑制体外细胞增殖/侵袭和体内肿瘤生长。机制上，转录组学分析表明DDX23参与了卵巢癌细胞mRNA的加工。具体来说，DDX23调控FOXM1的mRNA加工。DDX23沉默可减少卵巢癌中FOXM1的主要致癌转录物FOXM1C的产生，从而降低FOXM1蛋白的表达，减缓卵巢癌的恶性进展。营救实验表明FOXM1是ddx23诱导的卵巢癌恶性表型的关键执行者。此外，我们通过荧光素酶报告基因检测和染色质免疫沉淀（ChIP）检测证实了DDX23在卵巢癌中被转录因子（TF） E2F1转录激活。综上所述，我们的研究表明，DDX23高表达参与了卵巢癌的恶性行为，DDX23可能成为卵巢癌精准治疗的潜在靶点。
Ovarian carcinoma remains the most lethal gynecological carcinoma. Abnormal expression of splicing factors is closely related to the occurrence and development of tumors. The DEAD-box RNA helicases are important members of the splicing factor family. However, their role in the occurrence and progression of ovarian cancer is still unclear. In this study, we identified DEAD-box helicase 23 (DDX23) as a key DEAD-box RNA helicase in ovarian cancer using bioinformatics methods. We determined that DDX23 was upregulated in ovarian cancer and its high expression predicted poor prognosis. Functional assays indicated that DDX23 silencing significantly impeded cell proliferation/invasion in vitro and tumor growth in vivo. Mechanistically, transcriptomic analysis showed that DDX23 was involved in mRNA processing in ovarian cancer cells. Specifically, DDX23 regulated the mRNA processing of FOXM1. DDX23 silencing reduced the production of FOXM1C, the major oncogenic transcript of FOXM1 in ovarian cancer, thereby decreasing the FOXM1 protein expression and attenuating the malignant progression of ovarian cancer. Rescue assays indicated that FOXM1 was a key executor in DDX23-induced malignant phenotype of ovarian cancer. Furthermore, we confirmed that DDX23 was transcriptionally activated by the transcription factor (TF) E2F1 in ovarian cancer using luciferase reporter assays and chromatin immunoprecipitation (ChIP) assays. In conclusion, our study demonstrates that high DDX23 expression is involved in malignant behavior of ovarian cancer and DDX23 may become a potential target for precision therapy of ovarian cancer.
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影响因子：
9
作者：
He C;Li A;Lai Q;Ding J;Yan Q;Liu S;Li Q
通讯作者：
Li Q
DOI：
10.1038/nrc4019
发表时间：
2015-11
期刊：
Nature reviews. Cancer
影响因子：
--
作者：
Bowtell DD;Böhm S;Ahmed AA;Aspuria PJ;Bast RC Jr;Beral V;Berek JS;Birrer MJ;Blagden S;Bookman MA;Brenton JD;Chiappinelli KB;Martins FC;Coukos G;Drapkin R;Edmondson R;Fotopoulou C;Gabra H;Galon J;Gourley C;Heong V;Huntsman DG;Iwanicki M;Karlan BY;Kaye A;Lengyel E;Levine DA;Lu KH;McNeish IA;Menon U;Narod SA;Nelson BH;Nephew KP;Pharoah P;Powell DJ Jr;Ramos P;Romero IL;Scott CL;Sood AK;Stronach EA;Balkwill FR
通讯作者：
Balkwill FR
影响因子：
11.2
作者：
Kong X;Li L;Li Z;Le X;Huang C;Jia Z;Cui J;Huang S;Wang L;Xie K
通讯作者：
Xie K
影响因子：
8
作者：
Chan DW;Hui WW;Wang JJ;Yung MM;Hui LM;Qin Y;Liang RR;Leung TH;Xu D;Chan KK;Yao KM;Tsang BK;Ngan HY
通讯作者：
Ngan HY
影响因子：
8
作者：
He, X.;Arslan, A. D.;Pool, M. D.;Ho, T-T;Darcy, K. M.;Coon, J. S.;Beck, W. T.
通讯作者：
Beck, W. T.