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Splicing factor BUD31 promotes ovarian cancer progression through sustaining the expression of anti-apoptotic BCL2L12

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  • Zixiang Wang

    (Shandong University
    Shandong University)

  • Shourong Wang

    (Shandong University)

  • Junchao Qin

    (Shandong University
    Shandong University)

  • Xiyu Zhang

    (Shandong University)

  • Gang Lu

    (The Chinese University of Hong Kong)

  • Hongbin Liu

    (Shandong University)

  • Haiyang Guo

    (The Second Hospital of Shandong University, Cheeloo College of Medicine, Shandong University)

  • Ligang Wu

    (Chinese Academy of Sciences)

  • Victoria O. Shender

    (Federal Research and Clinical Center of Physical-Chemical Medicine of Federal Medical Biological Agency)

  • Changshun Shao

    (Soochow University)

  • Beihua Kong

    (Shandong University)

  • Zhaojian Liu

    (Shandong University
    Shandong University)

Abstract

Dysregulated expression of splicing factors has important roles in cancer development and progression. However, it remains a challenge to identify the cancer-specific splicing variants. Here we demonstrate that spliceosome component BUD31 is increased in ovarian cancer, and its higher expression predicts worse prognosis. We characterize the BUD31-binding motif and find that BUD31 preferentially binds exon-intron regions near splicing sites. Further analysis reveals that BUD31 inhibition results in extensive exon skipping and a reduced production of long isoforms containing full coding sequence. In particular, we identify BCL2L12, an anti-apoptotic BCL2 family member, as one of the functional splicing targets of BUD31. BUD31 stimulates the inclusion of exon 3 to generate full-length BCL2L12 and promotes ovarian cancer progression. Knockdown of BUD31 or splice-switching antisense oligonucleotide treatment promotes exon 3 skipping and results in a truncated isoform of BCL2L12 that undergoes nonsense-mediated mRNA decay, and the cells subsequently undergo apoptosis. Our findings reveal BUD31-regulated exon inclusion as a critical factor for ovarian cancer cell survival and cancer progression.

Suggested Citation

  • Zixiang Wang & Shourong Wang & Junchao Qin & Xiyu Zhang & Gang Lu & Hongbin Liu & Haiyang Guo & Ligang Wu & Victoria O. Shender & Changshun Shao & Beihua Kong & Zhaojian Liu, 2022. "Splicing factor BUD31 promotes ovarian cancer progression through sustaining the expression of anti-apoptotic BCL2L12," Nature Communications, Nature, vol. 13(1), pages 1-18, December.
  • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-34042-w
    DOI: 10.1038/s41467-022-34042-w
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    1. Victoria O. Shender & Ksenia S. Anufrieva & Polina V. Shnaider & Georgij P. Arapidi & Marat S. Pavlyukov & Olga M. Ivanova & Irina K. Malyants & Grigory A. Stepanov & Evgenii Zhuravlev & Rustam H. Zig, 2024. "Therapy-induced secretion of spliceosomal components mediates pro-survival crosstalk between ovarian cancer cells," Nature Communications, Nature, vol. 15(1), pages 1-26, December.

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