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剪接因子 WBP11 介导 MCM7 内含子保留以促进卵巢癌的恶性进展。

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

机构信息

Department of Obstetrics and Gynecology, Qilu Hospital of Shandong University, 107 Wenhua Xi Road, Ji'nan, 250012, Shandong, China.

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.

出版信息

Oncogene. 2024 May;43(20):1565-1578. doi: 10.1038/s41388-024-03015-2. Epub 2024 Apr 1.

Abstract

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.

摘要

越来越多的研究表明剪接因子在许多疾病中发挥着重要作用,包括人类癌症。我们的研究表明,剪接因子核心蛋白 WBP11 在卵巢癌(OC)组织中高度表达,并与预后不良相关。WBP11 抑制显著损害了卵巢癌细胞在体外和体内的增殖和迁移能力。此外,FOXM1 通过直接结合 OC 细胞中 WBP11 启动子转录激活 WBP11 的表达。重要的是,RNA-seq 和可变剪接事件分析显示,WBP11 沉默通过调节内含子 4 的保留降低了 MCM7 的表达。MCM7 抑制减弱了 WBP11 过表达 OC 细胞恶性行为的增加。总的来说,WBP11 被鉴定为一种致癌剪接因子,通过抑制 OC 细胞中 MCM7 内含子 4 的保留来促进恶性进展。因此,WBP11 是一种致癌剪接因子,在 OC 中具有潜在的治疗和预后意义。

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