AUTHOR=Zhao Chen , Li Yingwei , Qiu Chunping , Chen Jingying , Wu Huan , Wang Qiuman , Ma Xinyue , Song Kun , Kong Beihua TITLE=Splicing Factor DDX23, Transcriptionally Activated by E2F1, Promotes Ovarian Cancer Progression by Regulating FOXM1 JOURNAL=Frontiers in Oncology VOLUME=11 YEAR=2021 URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2021.749144 DOI=10.3389/fonc.2021.749144 ISSN=2234-943X ABSTRACT=

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.