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

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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 dellUniversità 2, Legnaro 35020, Padova, Italy

These authors contributed equally to this work.


Authors to whom correspondence should be addressed.

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 3UTR 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. View Full-Text

Keywords: γ-radiation; DNA Damage Response; miR-27a; ATM; A549 cells γ-radiation; DNA Damage Response; miR-27a; ATM; A549 cells

Autor: Andrea Di Francesco 1,†, Cristiano De Pittà 1,†, Francesca Moret 1, Vito Barbieri 2, Lucia Celotti 1,3,* and Maddalena Mognato 1,*



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