Exosome component 1 cleaves single-stranded DNA and sensitizes kidney renal clear cell carcinoma cells to poly(ADP-ribose) polymerase inhibitor

  1. Qiaoling Liu
  2. Qi Xiao
  3. Zhen Sun
  4. Bo Wang
  5. Lina Wang
  6. Na Wang
  7. Kai Wang
  8. Chengli Song
  9. Qingkai Yang  Is a corresponding author
  1. DaLian Medical University, China

Abstract

Targeting DNA repair pathway offers an important therapeutic strategy for Homo sapiens (human) cancers. However, the failure of DNA repair inhibitors to markedly benefit patients necessitates the development of new strategies. Here, we show that exosome component 1 (EXOSC1) promotes DNA damages and sensitizes human kidney renal clear cell carcinoma (KIRC) cells to DNA repair inhibitor. Considering that endogenous source of mutation (ESM) constantly assaults genomic DNA and likely sensitize human cancer cells to the inhibitor, we first analyzed the statistical relationship between the expression of individual genes and the mutations for KIRC. Among the candidates, EXOSC1 most notably promoted DNA damages and subsequent mutations via preferentially cleaving C site(s) in single-stranded DNA. Consistently, EXOSC1 was more significantly correlated with C>A transversions in coding strands than these in template strands in human KIRC. Notably, KIRC patients with high EXOSC1 showed a poor prognosis, and EXOSC1 sensitized human cancer cells to poly(ADP-ribose) polymerase inhibitor. These results show that EXOSC1 acts as an ESM in KIRC, and targeting EXOSC1 might be a potential therapeutic strategy.

Data availability

All data associated with this study are available in the main text or the supplementary materials.

The following previously published data sets were used

Article and author information

Author details

  1. Qiaoling Liu

    Institute of Cancer Stem Cell, DaLian Medical University, DaLian, China
    Competing interests
    The authors declare that no competing interests exist.
  2. Qi Xiao

    Institute of Cancer Stem Cell, DaLian Medical University, DaLian, China
    Competing interests
    The authors declare that no competing interests exist.
  3. Zhen Sun

    Institute of Cancer Stem Cell, DaLian Medical University, DaLian, China
    Competing interests
    The authors declare that no competing interests exist.
  4. Bo Wang

    Institute of Cancer Stem Cell, DaLian Medical University, DaLian, China
    Competing interests
    The authors declare that no competing interests exist.
  5. Lina Wang

    Institute of Cancer Stem Cell, DaLian Medical University, DaLian, China
    Competing interests
    The authors declare that no competing interests exist.
  6. Na Wang

    Institute of Cancer Stem Cell, DaLian Medical University, DaLian, China
    Competing interests
    The authors declare that no competing interests exist.
  7. Kai Wang

    Institute of Cancer Stem Cell, DaLian Medical University, DaLian, China
    Competing interests
    The authors declare that no competing interests exist.
  8. Chengli Song

    Institute of Cancer Stem Cell, DaLian Medical University, DaLian, China
    Competing interests
    The authors declare that no competing interests exist.
  9. Qingkai Yang

    Institute of Cancer Stem Cell, DaLian Medical University, DaLian, China
    For correspondence
    yangqingkai@dmu.edu.cn
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-6628-5393

Funding

National Natural Science Foundation of China (81872310)

  • Qingkai Yang

National Natural Science Foundation of China (82073123)

  • Chengli Song

China Postdoctoral Science Foundation (2020M680956)

  • Lina Wang

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Caigang Liu, Shengjing Hospital of China Medical University, China

Publication history

  1. Received: April 15, 2021
  2. Accepted: June 21, 2021
  3. Accepted Manuscript published: June 23, 2021 (version 1)
  4. Version of Record published: July 6, 2021 (version 2)

Copyright

© 2021, Liu et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Qiaoling Liu
  2. Qi Xiao
  3. Zhen Sun
  4. Bo Wang
  5. Lina Wang
  6. Na Wang
  7. Kai Wang
  8. Chengli Song
  9. Qingkai Yang
(2021)
Exosome component 1 cleaves single-stranded DNA and sensitizes kidney renal clear cell carcinoma cells to poly(ADP-ribose) polymerase inhibitor
eLife 10:e69454.
https://doi.org/10.7554/eLife.69454

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