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




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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 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,*

Fuente: http://mdpi.com/



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