Splicing factor BUD31 promotes ovarian cancer progression through sustaining the expression of anti-apoptotic BCL2L12
Zixiang Wang,
Shourong Wang,
Junchao Qin,
Xiyu Zhang,
Gang Lu,
Hongbin Liu,
Haiyang Guo,
Ligang Wu,
Victoria O. Shender,
Changshun Shao (shaoc@suda.edu.cn),
Beihua Kong (kongbeihua@sdu.edu.cn) and
Zhaojian Liu (liujian9782@sdu.edu.cn)
Additional contact information
Zixiang Wang: Shandong University
Shourong Wang: Shandong University
Junchao Qin: 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
Nature Communications, 2022, vol. 13, issue 1, 1-18
Abstract:
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.
Date: 2022
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-34042-w
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DOI: 10.1038/s41467-022-34042-w
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