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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
, 1,3,*  and 1,*
Received: 17 June 2013; in revised form: 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 which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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MDPI and ACS Style

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.

AMA Style

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. International Journal of Molecular Sciences. 2013; 14(9):17881-17896.

Chicago/Turabian Style

Di Francesco, Andrea; De Pittà, Cristiano; Moret, Francesca; Barbieri, Vito; Celotti, Lucia; Mognato, Maddalena. 2013. "The DNA-Damage Response to γ-Radiation Is Affected by miR-27a in A549 Cells." Int. J. Mol. Sci. 14, no. 9: 17881-17896.



Int. J. Mol. Sci. EISSN 1422-0067 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert