Genome-wide analysis of microRNA and gene expression profiles in human lymphocytes cultured in modeled microgravity during the DNA-damage response to γ-rays

Abstract

Perturbations during the DNA-damage response (DDR) originated from alteration of the microRNA-mediated gene regulation can contribute to carcinogenesis initiation. We analyzed the expression profile of microRNAs (miRNAs), which act as post-transcriptional regulators of gene expression, in human peripheral blood lymphocytes (PBLs) incubated in normal gravity (1g) and in modeled microgravity (MMG) during DDR induced by irradiation with γ-rays. We aimed at identifying radio-responsive miRNAs which were affected by MMG incubation during the repair time, altering the cellular response to ionizing radiation (IR). Our results show that miRNA expression profile is dose- and time-dependent in both gravity conditions and that MMG decreased the number of radio-responsive miRNAs. Moreover, we found that several miRNAs such as miR-27a, miR-144, miR-200a, miR-598, miR-650 were differentially expressed due to the combined action of IR and microgravity. Integrated analyses of miRNA and mRNA expression profiles carried out on PBLs derived from the same donors allowed to identify significant miRNA–mRNA anti-correlations of DDR-pathway. The transcripts of ATM and p53 genes were down-regulated in PBLs incubated in MMG during the repair time after IR, together with several anti-correlated genes of p53-pathway. Our findings demonstrate that simulated space flight conditions could influence miRNA expression profile altering the DDR to IR.