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Krämer, A. ; Anastasov, N. ; Angermeier, M. ; Winkler, K. ; Atkinson, M.J. ; Mörtl, S.

MicroRNA-mediated processes are essential for the cellular radiation response.

Radiat. Res. 176, 575-586 (2011)
Publ. Version/Full Text Research data DOI PMC
Open Access Green as soon as Postprint is submitted to ZB.
A detailed understanding of the mechanisms that determine the variable cellular sensitivity to radiation is needed for improved radiation therapy as well as for the identification of individuals with innate radiation hypersensitivity. MicroRNAs (miRNAs) are a class of small non-coding RNAs that post-transcriptionally regulate protein expression. Alterations in miRNA expression patterns in response to ionizing radiation have been shown, but there are almost no data describing the functional impact of these miRNA changes. We report here the results of studies on the functional roles of miRNAs in the radiation response in immortalized and primary endothelial cells. Global suppression of miRNA expression was achieved through downregulation of Argonaut e-2 (AGO2) or DICER proteins using RNAi. The reductions in either DICER or AGO2 led to increased cell death after irradiation, indicating a prosurvival function of miRNAs. Furthermore, while cell cycle checkpoint activation and apoptosis were compromised, DNA double-strand break repair was not affected by the lack of miRNAs. The differential sensitivity of these pathways implies the independent activation of the two response pathways rather than a concerted DNA damage response. The miRNAs that were changed after 2.5 Gy irradiation were identified by TaqMan-based low-density array technology. Of the miRNAs showing an upregulation 4 h or 24 h after radiation exposure, we were able to establish prosurvival and antiapoptotic functions for three miRNAs. Taken together, our data indicate a general prosurvival role for miRNA-mediated gene regulation during the radiation response. We show a functional association between miRNAs, apoptosis and cell cycle checkpoint activation in irradiated cells.
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Publication type Article: Journal article
Document type Scientific Article
Keywords no keywords
Language english
Publication Year 2011
HGF-reported in Year 2011
ISSN (print) / ISBN 0033-7587
e-ISSN 1938-5404
Journal Radiation Research
Quellenangaben Volume: 176, Issue: 5, Pages: 575-586 Article Number: , Supplement: ,
Publisher Radiation Research Society
Reviewing status Peer reviewed
Institute(s) Institute of Radiation Biology (ISB)
POF-Topic(s) 30202 - Environmental Health
Research field(s) Radiation Sciences
PSP Element(s) G-500200-001
PubMed ID 21854212
DOI 10.1667/RR2638.1
Scopus ID 80155141140
Erfassungsdatum 2011-11-14
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