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SNRPD2–CPSF7–UBE2K axis drives ovarian cancer progression via alternative splicing–polyadenylation crosstalk

Oncogene (2026) Cite this article

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Abstract

Aberrant alternative polyadenylation (APA) and alternative splicing (AS) contribute to numerous diseases, including cancer; however, their coordinated roles in ovarian cancer remain poorly understood. Here, we investigated CPSF7, an APA factor markedly upregulated in ovarian cancer and associated with poor prognosis. Silencing CPSF7 suppressed proliferation, migration, and invasion of ovarian cancer cells, while antisense oligonucleotides (ASOs) targeting CPSF7 reduced tumor growth in a patient‑derived xenograft (PDX) model. Mechanistically, knockdown of the splicing factor SNRPD2 induced exon 4 skipping in CPSF7 pre‑mRNA. Loss of exon 4 disrupted the RNA recognition motif (RRM) domain essential for CPSF7‑mediated pre‑mRNA cleavage and polyadenylation, and introduced premature termination codons (PTCs) that generated noncoding transcripts subject to nonsense‑mediated decay (NMD), thereby reducing CPSF7 expression. Thus, efficient splicing mediated by SNRPD2 is crucial for sustaining high CPSF7 levels in ovarian cancer cells. Functional assays showed that CPSF7 knockdown reduced proliferation and metastatic potential in cells with elevated SNRPD2, suggesting that CPSF7 is a key mediator of SNRPD2-driven oncogenesis. Moreover, CPSF7 governed specific APA events to maintain transcript stability, with UBE2K identified as a critical downstream target. CPSF7 preferentially bound distal polyadenylation signals (PASs) within the predominant UBE2K transcript (UBE2K-201), thereby increasing its mRNA stability and maintaining high functional UBE2K expression. Collectively, these findings reveal that AS and APA are interconnected in ovarian cancer via the SNRPD2–CPSF7–UBE2K axis, which drives disease progression and represents a promising target for therapeutic intervention.

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Fig. 1: CPSF7 is aberrantly overexpressed in ovarian cancer and correlates with poor patient prognosis.
The alternative text for this image may have been generated using AI.
Fig. 2: CPSF7 promotes proliferation, migration, and invasion of ovarian cancer cells.
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Fig. 3: CPSF7 functions as a key downstream effector of SNRPD2 in ovarian cancer.
The alternative text for this image may have been generated using AI.
Fig. 4: High SNRPD2 expression is associated with poor prognosis in ovarian cancer patients.
The alternative text for this image may have been generated using AI.
Fig. 5: Oncogenic role of SNRPD2 in driving ovarian cancer cell proliferation and metastasis.
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Fig. 6: SNRPD2 promotes CPSF7 exon 4 inclusion in ovarian cancer cells.
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Fig. 7: UBE2K is identified as a critical downstream target of CPSF7 in ovarian cancer cells.
The alternative text for this image may have been generated using AI.
Fig. 8: UBE2K mediates CPSF7 driven malignant progression in ovarian cancer.
The alternative text for this image may have been generated using AI.

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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. The authors would also like to express their sincere gratitude to Ms. Qi Qi for her valuable suggestions.

Funding

This study was supported by Shandong Provincial Natural Science Foundation (Grant No. ZR2023MH183), and Qingdao Natural Science Foundation (25-1-1-149-zyyd-jch).

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Author notes

  1. These authors contributed equally: Yingwei Li, Zhongshao Chen.

Authors and Affiliations

  1. Department of Obstetrics and Gynecology, Qilu Hospital of Shandong University. Medical Integration and Practice Center, Cheeloo College of Medicine, Shandong University, Shandong Key Laboratory of Reproductive Health and Birth Defects Prevention and Control, Ji’nan, 250012, China

    Yingwei Li

  2. Department of Obstetrics and Gynecology, Qilu Hospital of Shandong University, Shandong Key Laboratory of Reproductive Health and Birth Defects Prevention and Control, Ji’nan, 250012, China

    Zhongshao Chen, Qianqian Gao, Yuehan Gao, Yingying Pu & Ning Yang

  3. Department of Obstetrics and Gynecology, The Affiliated Hospital of Qingdao University, Qingdao, 266000, China

    Yuchao Diao

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Contributions

Conception and design: Yingwei Li. Methodology: Yingwei Li and Zhongshao Chen. Bioinformatics analysis: Yingwei Li. Acquisition of data: Zhongshao Chen, Yingying Pu, and Yuehan Gao. Analysis and interpretation of data: Zhongshao Chen, Yingying Pu, and Yuehan Gao. Technical, or material support: Qianqian Gao, Ning Yang, and Yuchao Diao. Study supervision: Yingwei Li. Writing, review, and/or revision of the manuscript: Yingwei Li and Zhongshao Chen. Final approval: All authors.

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Correspondence to Yingwei Li.

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Ethics Committee at Qilu Hospital of Shandong University approved the study (KYLL-202412-050). The Nude mouse xenograft assay and PDX model assay were approved by the Shandong University Animal Care and Use Committee (24045). All methods were performed in accordance with the relevant guidelines and regulations.

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Li, Y., Chen, Z., Diao, Y. et al. SNRPD2–CPSF7–UBE2K axis drives ovarian cancer progression via alternative splicing–polyadenylation crosstalk. Oncogene (2026). https://doi.org/10.1038/s41388-026-03812-x

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