analysis of mirna and mrna expression profiles highlights alterations in ionizing radiation response of human lymphocytes under modeled microgravitymicrorna和mrna表达谱分析凸显了电离辐射的变化响应模拟微重力下的人类淋巴细胞.pdfVIP

Analysis of miRNA and mRNA Expression Profiles Highlights Alterations in Ionizing Radiation Response of Human Lymphocytes under Modeled Microgravity 1. ` 1. 1 1 1 Cristina Girardi , Cristiano De Pitta , Silvia Casara , Gabriele Sales , Gerolamo Lanfranchi , Lucia 1,2 1 Celotti , Maddalena Mognato * ` 1 Dipartimento di Biologia, Universita degli Studi di Padova, Padova, Italy, 2 Laboratori Nazionali di Legnaro, INFN, Padova, Italy Abstract Background: Ionizing radiation (IR) can be extremely harmful for human cells since an improper DNA-damage response (DDR) to IR can contribute to carcinogenesis initiation. Perturbations in DDR pathway can originate from alteration in the functionality of the microRNA-mediated gene regulation, being microRNAs (miRNAs) small noncoding RNA that act as post- transcriptional regulators of gene expression. In this study we gained insight into the role of miRNAs in the regulation of DDR to IR under microgravity, a condition of weightlessness experienced by astronauts during space missions, which could have a synergistic action on cells, increasing the risk of radiation exposure. Methodology/Principal Findings: We analyzed miRNA expression profile of human peripheral blood lymphocytes (PBL) incubated for 4 and 24 h in normal gravity (1 g) and in modeled microgravity (MMG) during the repair time after irradiation with 0.2 and 2Gy of c-rays. Our results show that MMG alters miRNA expression signature of irradiated PBL by decreasing the number of radio-responsive miRNAs. Moreover, let-7i*, miR-7, miR-7-1*, miR-27a, miR-144, miR-200a, miR-598, miR-650 are deregulated by the combined action of radiatio