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.
Highlights
According to statistics from the American Cancer Society (ACS), ovarian cancer is the most lethal gynecological malignancy, ranking fifth among the mortality rates of female cancers [1]
Our previous study showed that USP39 functioned as an oncogenic splicing factor in ovarian cancer through maintaining efficient splicing of HMGA2 [13]
The DEAD-box RNA helicases are important members of the splicing factor family and they usually function as components of large multi-protein complexes and play essential roles in RNA processing including spliceosome biogenesis, miRNA biogenesis and splicing, which are crucial for cellular proliferation and transformation of tumorigenicity [40, 41]
Summary
According to statistics from the American Cancer Society (ACS), ovarian cancer is the most lethal gynecological malignancy, ranking fifth among the mortality rates of female cancers [1]. The five-year relative survival rate is generally between 30% and 40% [2]. High-grade serous ovarian carcinoma (HGSOC) has the highest incidence and aggressiveness of all subtypes, and accounts for 70-80% of ovarian cancer deaths [3, 4]. Current first-line treatments for ovarian cancer include both. DDX23 Promotes Proliferation and Invasion surgery and systemic treatment. The application of antiangiogenic agents and poly ADP-ribose polymerase (PARP) inhibitors has produced beneficial therapeutic effects for ovarian cancer patients [5, 6]. Despite the continued progress in diagnosis and treatment technologies, some patients still relapse in a short time. Further research is needed to gain new insights into the pathogenesis of ovarian cancer
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