Targeting DNA-PKcs and ATM with miR-101 sensitizes tumors to radiation

Dan Yan, Wooi Loon Ng, Xiangming Zhang, Ping Wang, Zhaobin Zhang, Yin Yuan Mo, Hui Mao, Chunhai Hao, Jeffrey J. Olson, Walter J. Curran, Ya Wang

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150 Scopus citations

Abstract

Background: Radiotherapy kills tumor-cells by inducing DNA double strand breaks (DSBs). However, the efficient repair of tumors frequently prevents successful treatment. Therefore, identifying new practical sensitizers is an essential step towards successful radiotherapy. In this study, we tested the new hypothesis: identifying the miRNAs to target DNA DSB repair genes could be a new way for sensitizing tumors to ionizing radiation. Principal Findings: Here, we chose two genes: DNA-PKcs (an essential factor for non-homologous end-joining repair) and ATM (an important checkpoint regulator for promoting homologous recombination repair) as the targets to search their regulating miRNAs. By combining the database search and the bench work, we picked out miR-101. We identified that miR-101 could efficiently target DNA-PKcs and ATM via binding to the 3'- UTR of DNA-PKcs or ATM mRNA. Up-regulating miR-101 efficiently reduced the protein levels of DNA-PKcs and ATM in these tumor cells and most importantly, sensitized the tumor cells to radiation in vitro and in vivo. Conclusions: These data demonstrate for the first time that miRNAs could be used to target DNA repair genes and thus sensitize tumors to radiation. These results provide a new way for improving tumor radiotherapy.

Original languageEnglish (US)
Article numbere11397
JournalPLoS ONE
Volume5
Issue number7
DOIs
StatePublished - Aug 13 2010

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ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

Cite this

Yan, D., Ng, W. L., Zhang, X., Wang, P., Zhang, Z., Mo, Y. Y., Mao, H., Hao, C., Olson, J. J., Curran, W. J., & Wang, Y. (2010). Targeting DNA-PKcs and ATM with miR-101 sensitizes tumors to radiation. PLoS ONE, 5(7), [e11397]. https://doi.org/10.1371/journal.pone.0011397