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

Research output: Contribution to journalArticle

148 Citations (Scopus)

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
Externally publishedYes

Fingerprint

Automatic teller machines
Tumors
Radiation
neoplasms
Repair
DNA
radiotherapy
Radiotherapy
MicroRNAs
Neoplasms
Double-Stranded DNA Breaks
Genes
Cells
genes
homologous recombination
Recombinational DNA Repair
3' untranslated regions
DNA repair
ionizing radiation
Ionizing radiation

ASJC Scopus subject areas

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

Cite this

Yan, D., Ng, W. L., Zhang, X., Wang, P., Zhang, Z., Mo, Y. Y., ... 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

Targeting DNA-PKcs and ATM with miR-101 sensitizes tumors to radiation. / Yan, Dan; Ng, Wooi Loon; Zhang, Xiangming; Wang, Ping; Zhang, Zhaobin; Mo, Yin Yuan; Mao, Hui; Hao, Chunhai; Olson, Jeffrey J.; Curran, Walter J.; Wang, Ya.

In: PLoS ONE, Vol. 5, No. 7, e11397, 13.08.2010.

Research output: Contribution to journalArticle

Yan, D, Ng, WL, Zhang, X, Wang, P, Zhang, Z, Mo, YY, Mao, H, Hao, C, Olson, JJ, Curran, WJ & Wang, Y 2010, 'Targeting DNA-PKcs and ATM with miR-101 sensitizes tumors to radiation', PLoS ONE, vol. 5, no. 7, e11397. https://doi.org/10.1371/journal.pone.0011397
Yan D, Ng WL, Zhang X, Wang P, Zhang Z, Mo YY et al. Targeting DNA-PKcs and ATM with miR-101 sensitizes tumors to radiation. PLoS ONE. 2010 Aug 13;5(7). e11397. https://doi.org/10.1371/journal.pone.0011397
Yan, Dan ; Ng, Wooi Loon ; Zhang, Xiangming ; Wang, Ping ; Zhang, Zhaobin ; Mo, Yin Yuan ; Mao, Hui ; Hao, Chunhai ; Olson, Jeffrey J. ; Curran, Walter J. ; Wang, Ya. / Targeting DNA-PKcs and ATM with miR-101 sensitizes tumors to radiation. In: PLoS ONE. 2010 ; Vol. 5, No. 7.
@article{c963a621ccdc4c8195a311d18d25cb20,
title = "Targeting DNA-PKcs and ATM with miR-101 sensitizes tumors to radiation",
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.",
author = "Dan Yan and Ng, {Wooi Loon} and Xiangming Zhang and Ping Wang and Zhaobin Zhang and Mo, {Yin Yuan} and Hui Mao and Chunhai Hao and Olson, {Jeffrey J.} and Curran, {Walter J.} and Ya Wang",
year = "2010",
month = "8",
day = "13",
doi = "10.1371/journal.pone.0011397",
language = "English (US)",
volume = "5",
journal = "PLoS One",
issn = "1932-6203",
publisher = "Public Library of Science",
number = "7",

}

TY - JOUR

T1 - Targeting DNA-PKcs and ATM with miR-101 sensitizes tumors to radiation

AU - Yan, Dan

AU - Ng, Wooi Loon

AU - Zhang, Xiangming

AU - Wang, Ping

AU - Zhang, Zhaobin

AU - Mo, Yin Yuan

AU - Mao, Hui

AU - Hao, Chunhai

AU - Olson, Jeffrey J.

AU - Curran, Walter J.

AU - Wang, Ya

PY - 2010/8/13

Y1 - 2010/8/13

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=77958133262&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=77958133262&partnerID=8YFLogxK

U2 - 10.1371/journal.pone.0011397

DO - 10.1371/journal.pone.0011397

M3 - Article

C2 - 20617180

AN - SCOPUS:77958133262

VL - 5

JO - PLoS One

JF - PLoS One

SN - 1932-6203

IS - 7

M1 - e11397

ER -