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

International Journal of Molecular Sciences

Andrea Di Francesco¹  Cristiano De Pitt๠ Francesca Moret¹  Vito Barbieri²  Lucia Celotti¹ 

[1] Department of Biology, University of Padova, via U. Bassi 58/B, Padova 35131, Italy; E-Mails:;Department of Surgery, Oncology and Gastroenterology, University of Padova via Gattamelata 64, Padova 35128, Italy; E-Mail:

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

DOI  :  10.3390/ijms140917881

来源: mdpi

【 摘 要 】

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.

【 授权许可】

CC BY   
© 2013 by the authors; licensee MDPI, Basel, Switzerland