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

Oncogene (2024)Cite this article

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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.

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Fig. 1: WBP11 is upregulated in OC and indicates poor prognosis.
Fig. 2: WBP11 promotes proliferation, migration and invasion of ovarian cancer cells.
Fig. 3: Knockdown of WBP11 suppresses xenograft tumor growth in vivo.
Fig. 4: FOXM1 activates WBP11 transcription in OC cells.
Fig. 5: MCM7 functions as a downstream target of WBP11 based on RNA-seq analysis.
Fig. 6: WBP11 facilitates efficient splicing of MCM7 intron.
Fig. 7: Knockdown of MCM7 impaired the phenotype of WBP11 overexpression.
Fig. 8: ASO-mediated MCM7 knockdown suppresses the proliferation and mobility of OC cells.

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Data availability

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Acknowledgements

We thank American Journal Experts (AJE) for English language editing. Figdraw was used for image production.

Funding

This work was supported by National Key Technology Research and Development Programme of China (2022YFC2704200 and 2022YFC2704202) and Natural Science Foundation of Shandong Province (ZR2023MH183).

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Authors and Affiliations

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

    Yuan Wei, Zhongshao Chen & Kun Song

  2. 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

    Yingwei Li

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Contributions

Conception and design: YL, KS. Methodology: YL. Acquisition of data: YW, YL, ZC. Analysis and interpretation of data: YW, YL. Administrative, technical, or material support: YL, KS. Study supervision: YL, KS. Writing, review, and/or revision of the manuscript: YW, YL, KS. Final approval: All authors.

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Correspondence to Yingwei Li or Kun Song.

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Ethical approval was obtained from the Ethics Committee of Qilu Hospital, Shandong University (KYLL-202209-032).

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Wei, Y., Chen, Z., Li, Y. et al. The splicing factor WBP11 mediates MCM7 intron retention to promote the malignant progression of ovarian cancer. Oncogene (2024). https://doi.org/10.1038/s41388-024-03015-2

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