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Author Notes:

To whom correspondence should be addressed: Dept. of Radiation Oncology, Emory University School of Medicine, 1365 Clifton Rd., NE, Atlanta, GA 30322., Tel.: 404-778-1832; Fax: 404-778-1750; E-mail: ywang94@emory.edu

Y. W. designed the study.

B. H., X. W., S. H., X. Y., P. W., X. Z., J. W., and H. W. conceived and performed the experiments.

B. H., X. W., and Y. W. analyzed data and prepared the manuscript.

All authors reviewed and approved the manuscript.

We thank Drs. Eric Olson, James Woodgett, Chenguang Wang, Maria Jasin, Eric Hendrickson, Tej Pandita, John Mina, and Jiri Bartek for providing reagents; members of the Wang laboratory for helpful discussion; and Doreen Theune for editing the manuscript

The authors declare that they have no conflicts of interest with the contents of this article.

The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.


Research Funding:

The Winship Cancer Institute of Emory University was supported by National Institutes of Health Grant P30CA138292.

This work was supported by National Institutes of Health Grants CA186129 and CA185882 (to Y. W.) and P30CA138292 (to Winship Institute).

This work was also supported by China National High Technology Research and Development Program Grant 2014AA020604 (to X. Y.).


  • Science & Technology
  • Life Sciences & Biomedicine
  • Biochemistry & Molecular Biology
  • cellular regulation
  • DNA repair
  • DNA-dependent serine
  • threonine protein kinase (DNA-PK)
  • microRNA (miRNA)
  • radiation biology
  • miR-21
  • ionizing radiation
  • DNA double strand breaks
  • GSK3
  • non-homologous end-joining
  • homologous recombination repair

miR-21-mediated Radioresistance Occurs via Promoting Repair of DNA Double Strand Breaks*


Journal Title:

Journal of Biological Chemistry


Volume 292, Number 8


, Pages 3531-3540

Type of Work:

Article | Final Publisher PDF


miR-21, as an oncogene that overexpresses in most human tumors, is involved in radioresistance; however, the mechanism remains unclear. Here, we demonstrate that miR-21-mediated radioresistance occurs through promoting repair of DNA double strand breaks, which includes facilitating both non-homologous end-joining (NHEJ) and homologous recombination repair (HRR). The miR-21-promoted NHEJ occurs through targeting GSK3B (a novel target of miR-21), which affects the CRY2/PP5 pathway and in turn increases DNA-PKcs activity. The miR-21-promoted HRR occurs through targeting both GSK3B and CDC25A (a known target of miR-21), which neutralizes the effects of targeting GSK3B-induced CDC25A increase because GSK3B promotes degradation of both CDC25A and cyclin D1, but CDC25A and cyclin D1 have an opposite effect on HRR. A negative correlation of expression levels between miR-21 and GSK3β exists in a subset of human tumors. Our results not only elucidate miR-21-mediated radioresistance, but also provide potential new targets for improving radiotherapy.

Copyright information:

© 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

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