The splicing factor WBP11 mediates MCM7 intron retention to promote the malignant progression of ovarian cancer.

Autor: Wei Y; Department of Obstetrics and Gynecology, Qilu Hospital of Shandong University, 107 Wenhua Xi Road, Ji'nan, 250012, Shandong, China., Chen Z; Department of Obstetrics and Gynecology, Qilu Hospital of Shandong University, 107 Wenhua Xi Road, Ji'nan, 250012, Shandong, China., Li Y; Department of Obstetrics and Gynecology, Qilu Hospital of Shandong University, Medical Integration and Practice Center, Cheeloo College of Medicine, Shandong University, Ji'nan, 250012, Shandong, China. sduliyingwei@126.com., Song K; Department of Obstetrics and Gynecology, Qilu Hospital of Shandong University, 107 Wenhua Xi Road, Ji'nan, 250012, Shandong, China. songkun2001226@sdu.edu.cn.
Jazyk: angličtina
Zdroj: Oncogene [Oncogene] 2024 May; Vol. 43 (20), pp. 1565-1578. Date of Electronic Publication: 2024 Apr 01.
DOI: 10.1038/s41388-024-03015-2
Abstrakt: Accumulating studies suggest that splicing factors play important roles in many diseases including human cancers. Our study revealed that WBP11, a core splicing factor, is highly expressed in ovarian cancer (OC) tissues and associated with a poor prognosis. WBP11 inhibition significantly impaired the proliferation and mobility of ovarian cancer cells in vitro and in vivo. Furthermore, FOXM1 transcriptionally activated WBP11 expression by directly binding to its promoter in OC cells. Importantly, RNA-seq and alternative splicing event analysis revealed that WBP11 silencing decreased the expression of MCM7 by regulating intron 4 retention. MCM7 inhibition attenuated the increase in malignant behaviors of WBP11-overexpressing OC cells. Overall, WBP11 was identified as an oncogenic splicing factor that contributes to malignant progression by repressing intron 4 retention of MCM7 in OC cells. Thus, WBP11 is an oncogenic splicing factor with potential therapeutic and prognostic implications in OC.
(© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)
Databáze: MEDLINE
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