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The DNA-Damage Response to γ-Radiation Is Affected by miR-27a in A549 Cells
Department of Biology, University of Padova, via U. Bassi 58/B, Padova 35131, Italy
Department of Surgery, Oncology and Gastroenterology, University of Padova via Gattamelata 64, Padova 35128, Italy
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; in revised form: 2 August 2013 / Accepted: 7 August 2013 / Published: 2 September 2013
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
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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.
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.
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.