title: The DNA-damage response to γ-radiation is affected by miR-27a in A549 cells.
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.
authors.affiliation: Department of Biology, University of Padova, via U. Bassi 58/B, Padova 35131, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Di Francesco
authors.forename: Cristiano
authors.initials: C
authors.lastname: De Pittà
authors.forename: Francesca
authors.initials: F
authors.lastname: Moret
authors.forename: Vito
authors.initials: V
authors.lastname: Barbieri
authors.forename: Lucia
authors.initials: L
authors.lastname: Celotti
authors.forename: Maddalena
authors.initials: M
authors.lastname: Mognato
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D064007:Ataxia Telangiectasia Mutated Proteins / Q000235:genetics; D002460:Cell Line; D004249:DNA Damage / Q000528:radiation effects; D005720:Gamma Rays / Q000009:adverse effects*; D006801:Humans; D035683:MicroRNAs / Q000235:genetics
chemical_list: D020413:3' Untranslated Regions; C531388:MIRN27 microRNA, human; D035683:MicroRNAs; D064007:Ataxia Telangiectasia Mutated Proteins