Next-generation sequencing analysis of circulating micro-RNA expression in response to parabolic flight as a spaceflight analogue

Abstract

Understanding physiologic reactions to weightlessness is an indispensable requirement for safe human space missions. This study aims to analyse changes in the expression of circulating miRNAs following exposure to gravitational changes. Eight healthy volunteers (age: 24.5 years, male: 4, female: 4) were included. Each subject underwent 31 short-term phases of weightlessness and hypergravity induced by parabolic flight as a spaceflight analogue. At baseline, 1 and 24 h after parabolic flight, venous blood was withdrawn. Analysis of circulating miRNAs in serum was conducted by means of next generation sequencing. In total, 213 miRNAs were robustly detected (TPM > 5) by small RNA sequencing in all 24 samples. Four miRNAs evidenced a significant change in expression after adjusting for multiple testing. Only miR-223-3p showed a consistent significant decrease 24 h after parabolic flight compared to baseline values and values at 1 h after parabolic flight. miR-941 and miR-24-3p showed a significant decrease 24 h after parabolic flight compared to 1 h after parabolic flight but not to baseline values. miR-486-5p showed a significant increase 24 h after parabolic flight compared to 1 h after parabolic flight but not to baseline values. A target network analysis identified genes of the p53 signaling pathway and the cell cycle highly enriched among the targets of the four microRNAs. Our findings suggest cellular adaption to gravitational changes at the post-transcriptional level. Based on our results, we suggest a change in cell cycle regulation as potential explanation for adaptational changes observed in space missions.