IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v13y2022i1d10.1038_s41467-022-34042-w.html
   My bibliography  Save this article

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

Author

Listed:
  • 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
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-022-34042-w
    File Function: Abstract
    Download Restriction: no

    File URL: https://libkey.io/10.1038/s41467-022-34042-w?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    References listed on IDEAS

    as
    1. Jackson S. Turner & Jane A. O’Halloran & Elizaveta Kalaidina & Wooseob Kim & Aaron J. Schmitz & Julian Q. Zhou & Tingting Lei & Mahima Thapa & Rita E. Chen & James Brett Case & Fatima Amanat & Adriana, 2021. "SARS-CoV-2 mRNA vaccines induce persistent human germinal centre responses," Nature, Nature, vol. 596(7870), pages 109-113, August.
    2. Akira Yokoi & Yusuke Yoshioka & Yusuke Yamamoto & Mitsuya Ishikawa & Shun-ichi Ikeda & Tomoyasu Kato & Tohru Kiyono & Fumitaka Takeshita & Hiroaki Kajiyama & Fumitaka Kikkawa & Takahiro Ochiya, 2017. "Malignant extracellular vesicles carrying MMP1 mRNA facilitate peritoneal dissemination in ovarian cancer," Nature Communications, Nature, vol. 8(1), pages 1-15, April.
    3. Esmee Koedoot & Michiel Fokkelman & Vasiliki-Maria Rogkoti & Marcel Smid & Iris Sandt & Hans Bont & Chantal Pont & Janna E. Klip & Steven Wink & Mieke A. Timmermans & Erik A. C. Wiemer & Peter Stoilov, 2019. "Uncovering the signaling landscape controlling breast cancer cell migration identifies novel metastasis driver genes," Nature Communications, Nature, vol. 10(1), pages 1-16, December.
    4. Hyoung Kim & Haineng Xu & Erin George & Dorothy Hallberg & Sushil Kumar & Veena Jagannathan & Sergey Medvedev & Yasuto Kinose & Kyle Devins & Priyanka Verma & Kevin Ly & Yifan Wang & Roger A. Greenber, 2020. "Combining PARP with ATR inhibition overcomes PARP inhibitor and platinum resistance in ovarian cancer models," Nature Communications, Nature, vol. 11(1), pages 1-16, December.
    5. Daichi Inoue & Guo-Liang Chew & Bo Liu & Brittany C. Michel & Joseph Pangallo & Andrew R. D’Avino & Tyler Hitchman & Khrystyna North & Stanley Chun-Wei Lee & Lillian Bitner & Ariele Block & Amanda R. , 2019. "Spliceosomal disruption of the non-canonical BAF complex in cancer," Nature, Nature, vol. 574(7778), pages 432-436, October.
    Full references (including those not matched with items on IDEAS)

    Citations

    Citations are extracted by the CitEc Project, subscribe to its RSS feed for this item.
    as


    Cited by:

    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.

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Ankita Leekha & Arash Saeedi & Monish Kumar & K. M. Samiur Rahman Sefat & Melisa Martinez-Paniagua & Hui Meng & Mohsen Fathi & Rohan Kulkarni & Kate Reichel & Sujit Biswas & Daphne Tsitoura & Xinli Li, 2024. "An intranasal nanoparticle STING agonist protects against respiratory viruses in animal models," Nature Communications, Nature, vol. 15(1), pages 1-21, December.
    2. Jonathan P. Ling & Alexei M. Bygrave & Clayton P. Santiago & Rogger P. Carmen-Orozco & Vickie T. Trinh & Minzhong Yu & Yini Li & Ying Liu & Kyra D. Bowden & Leighton H. Duncan & Jeong Han & Kamil Tane, 2022. "Cell-specific regulation of gene expression using splicing-dependent frameshifting," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    3. Jun Dai & Shuyu Zheng & Matías M. Falco & Jie Bao & Johanna Eriksson & Sanna Pikkusaari & Sofia Forstén & Jing Jiang & Wenyu Wang & Luping Gao & Fernando Perez-Villatoro & Olli Dufva & Khalid Saeed & , 2024. "Tracing back primed resistance in cancer via sister cells," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
    4. Taichi Igarashi & Marianne Mazevet & Takaaki Yasuhara & Kimiyoshi Yano & Akifumi Mochizuki & Makoto Nishino & Tatsuya Yoshida & Yukihiro Yoshida & Nobuhiko Takamatsu & Akihide Yoshimi & Kouya Shiraish, 2023. "An ATR-PrimPol pathway confers tolerance to oncogenic KRAS-induced and heterochromatin-associated replication stress," Nature Communications, Nature, vol. 14(1), pages 1-22, December.
    5. Emanuele Andreano & Ida Paciello & Silvia Marchese & Lorena Donnici & Giulio Pierleoni & Giulia Piccini & Noemi Manganaro & Elisa Pantano & Valentina Abbiento & Piero Pileri & Linda Benincasa & Ginevr, 2022. "Anatomy of Omicron BA.1 and BA.2 neutralizing antibodies in COVID-19 mRNA vaccinees," Nature Communications, Nature, vol. 13(1), pages 1-8, December.
    6. Vincent Pavot & Catherine Berry & Michael Kishko & Natalie G. Anosova & Lu Li & Tim Tibbitts & Dean Huang & Alice Raillard & Sylviane Gautheron & Cindy Gutzeit & Marguerite Koutsoukos & Roman M. Chicz, 2023. "Beta variant COVID-19 protein booster vaccine elicits durable cross-neutralization against SARS-CoV-2 variants in non-human primates," Nature Communications, Nature, vol. 14(1), pages 1-8, December.
    7. Julia Merkenschlager & Riza-Maria Berz & Victor Ramos & Maximilian Uhlig & Andrew J. MacLean & Carla R. Nowosad & Thiago Y. Oliveira & Michel C. Nussenzweig, 2023. "Continually recruited naïve T cells contribute to the follicular helper and regulatory T cell pools in germinal centers," Nature Communications, Nature, vol. 14(1), pages 1-11, December.
    8. Guidantonio Malagoli Tagliazucchi & Anna J. Wiecek & Eloise Withnell & Maria Secrier, 2023. "Genomic and microenvironmental heterogeneity shaping epithelial-to-mesenchymal trajectories in cancer," Nature Communications, Nature, vol. 14(1), pages 1-20, December.
    9. Caroline Gubser Keller & Youngah Shin & Alex Mas Monteys & Nicole Renaud & Martin Beibel & Natalia Teider & Thomas Peters & Thomas Faller & Sophie St-Cyr & Judith Knehr & Guglielmo Roma & Alejandro Re, 2022. "An orally available, brain penetrant, small molecule lowers huntingtin levels by enhancing pseudoexon inclusion," Nature Communications, Nature, vol. 13(1), pages 1-11, December.
    10. Z. L. Liu & X. Y. Meng & R. J. Bao & M. Y. Shen & J. J. Sun & W. D. Chen & F. Liu & Y. He, 2024. "Single cell deciphering of progression trajectories of the tumor ecosystem in head and neck cancer," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
    11. Wei Liu & Hongchao Cao & Jing Wang & Areeg Elmusrati & Bing Han & Wei Chen & Ping Zhou & Xiyao Li & Stephen Keysar & Antonio Jimeno & Cun-Yu Wang, 2024. "Histone-methyltransferase KMT2D deficiency impairs the Fanconi anemia/BRCA pathway upon glycolytic inhibition in squamous cell carcinoma," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
    12. Arnaud Desrosiers & Rabeb Mouna Derbali & Sami Hassine & Jérémie Berdugo & Valérie Long & Dominic Lauzon & Vincent De Guire & Céline Fiset & Luc DesGroseillers & Jeanne Leblond Chain & Alexis Vallée-B, 2022. "Programmable self-regulated molecular buffers for precise sustained drug delivery," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
    13. Ivan T. Lee & Raffael Nachbagauer & David Ensz & Howard Schwartz & Lizbeth Carmona & Kristi Schaefers & Andrei Avanesov & Daniel Stadlbauer & Carole Henry & Ren Chen & Wenmei Huang & Daniela Ramirez S, 2023. "Safety and immunogenicity of a phase 1/2 randomized clinical trial of a quadrivalent, mRNA-based seasonal influenza vaccine (mRNA-1010) in healthy adults: interim analysis," Nature Communications, Nature, vol. 14(1), pages 1-11, December.
    14. Jernej Pušnik & Werner O. Monzon-Posadas & Jasmin Zorn & Kathrin Peters & Maximilian Baum & Hannah Proksch & Celina Beta Schlüter & Galit Alter & Tanja Menting & Hendrik Streeck, 2023. "SARS-CoV-2 humoral and cellular immunity following different combinations of vaccination and breakthrough infection," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
    15. Marta Ferreira-Gomes & Yidan Chen & Pawel Durek & Hector Rincon-Arevalo & Frederik Heinrich & Laura Bauer & Franziska Szelinski & Gabriela Maria Guerra & Ana-Luisa Stefanski & Antonia Niedobitek & Ann, 2024. "Recruitment of plasma cells from IL-21-dependent and IL-21-independent immune reactions to the bone marrow," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    16. Laura Pérez-Alós & Jose Juan Almagro Armenteros & Johannes Roth Madsen & Cecilie Bo Hansen & Ida Jarlhelt & Sebastian Rask Hamm & Line Dam Heftdal & Mia Marie Pries-Heje & Dina Leth Møller & Kamille F, 2022. "Modeling of waning immunity after SARS-CoV-2 vaccination and influencing factors," Nature Communications, Nature, vol. 13(1), pages 1-11, December.
    17. Sophie A. Herbst & Mattias Vesterlund & Alexander J. Helmboldt & Rozbeh Jafari & Ioannis Siavelis & Matthias Stahl & Eva C. Schitter & Nora Liebers & Berit J. Brinkmann & Felix Czernilofsky & Tobias R, 2022. "Proteogenomics refines the molecular classification of chronic lymphocytic leukemia," Nature Communications, Nature, vol. 13(1), pages 1-18, December.
    18. Philipe Gobeil & Stéphane Pillet & Iohann Boulay & Nathalie Charland & Aurélien Lorin & Matthew P. Cheng & Donald C. Vinh & Philippe Boutet & Robbert Most & François Roman & Maria Angeles Ceregido & N, 2022. "Durability and cross-reactivity of immune responses induced by a plant-based virus-like particle vaccine for COVID-19," Nature Communications, Nature, vol. 13(1), pages 1-10, December.
    19. Hassen Kared & Asia-Sophia Wolf & Amin Alirezaylavasani & Anthony Ravussin & Guri Solum & Trung The Tran & Fridtjof Lund-Johansen & John Torgils Vaage & Lise Sofie Nissen-Meyer & Unni C. Nygaard & Ola, 2022. "Immune responses in Omicron SARS-CoV-2 breakthrough infection in vaccinated adults," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
    20. Elena Giudice & Tzu-Ting Huang & Jayakumar R. Nair & Grant Zurcher & Ann McCoy & Darryl Nousome & Marc R. Radke & Elizabeth M. Swisher & Stanley Lipkowitz & Kristen Ibanez & Duncan Donohue & Tyler Mal, 2024. "The CHK1 inhibitor prexasertib in BRCA wild-type platinum-resistant recurrent high-grade serous ovarian carcinoma: a phase 2 trial," Nature Communications, Nature, vol. 15(1), pages 1-14, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-34042-w. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.