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Int. J. Mol. Sci. 2013, 14(9), 17881-17896; doi:10.3390/ijms140917881
Article

The DNA-Damage Response to γ-Radiation Is Affected by miR-27a in A549 Cells

1,†
,
1,†
,
1
,
2
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1,3,*  and 1,*
1 Department of Biology, University of Padova, via U. Bassi 58/B, Padova 35131, Italy 2 Department of Surgery, Oncology and Gastroenterology, University of Padova via Gattamelata 64, Padova 35128, Italy 3 INFN-Laboratori Nazionali di Legnaro, Viale dell'Università 2, Legnaro 35020, Padova, Italy These authors contributed equally to this work.
* Authors to whom correspondence should be addressed.
Received: 17 June 2013 / Revised: 2 August 2013 / Accepted: 7 August 2013 / Published: 2 September 2013
(This article belongs to the collection Radiation Toxicity in Cells)
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Abstract

Perturbations during the cell DNA-Damage Response (DDR) can originate from alteration in the functionality of the microRNA-mediated gene regulation, being microRNAs (miRNAs), small non-coding RNAs that act as post-transcriptional regulators of gene expression. The oncogenic miR-27a is over-expressed in several tumors and, in the present study, we investigated its interaction with ATM, the gene coding for the main kinase of DDR pathway. Experimental validation to confirm miR-27a as a direct regulator of ATM was performed by site-direct mutagenesis of the luciferase reporter vector containing the 3'UTR of ATM gene, and by miRNA oligonucleotide mimics. We then explored the functional miR-27a/ATM interaction under biological conditions, i.e., during the response of A549 cells to ionizing radiation (IR) exposure. To evaluate if miR-27a over-expression affects IR-induced DDR activation in A549 cells we determined cell survival, cell cycle progression and DNA double-strand break (DSB) repair. Our results show that up-regulation of miR-27a promotes cell proliferation of non-irradiated and irradiated cells. Moreover, increased expression of endogenous mature miR-27a in A549 cells affects DBS rejoining kinetics early after irradiation.
Keywords: γ-radiation; DNA Damage Response; miR-27a; ATM; A549 cells γ-radiation; DNA Damage Response; miR-27a; ATM; A549 cells
This is an open access article distributed under the Creative Commons Attribution License (CC BY 3.0).
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Di Francesco, A.; De Pittà, C.; Moret, F.; Barbieri, V.; Celotti, L.; Mognato, M. The DNA-Damage Response to γ-Radiation Is Affected by miR-27a in A549 Cells. Int. J. Mol. Sci. 2013, 14, 17881-17896.

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