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 At baseline, 1 and 24 h after parabolic flight, venous blood was withdrawn.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.

了解失重状态下的生理反应是安全载人航天任务不可或缺的要求。本研究旨在分析暴露于重力变化后循环 miRNA 表达的变化。纳入8名健康志愿者（年龄：24.5岁，男性：4名，女性：4名）。每个受试者都经历了 31 个由抛物线飞行（类似于太空飞行）引起的短期失重和超重力阶段。在基线、抛物线飞行后 1 小时和 24 小时，抽取静脉血。通过下一代测序对血清中的循环 miRNA 进行分析。通过小 RNA 测序，在所有 24 个样本中总共检测到了 213 个 miRNA（TPM > 5）。经过多次测试调整后，四种 miRNA 的表达发生了显着变化。与基线值和抛物线飞行后 1 小时的值相比，仅 miR-223-3p 在抛物线飞行后 24 小时表现出一致的显着下降。与抛物线飞行后 1 小时相比，miR-941 和 miR-24-3p 在抛物线飞行后 24 小时显示出显着下降，但未达到基线值。与抛物线飞行后 1 小时相比，miR-486-5p 在抛物线飞行后 24 小时显示显着增加，但未达到基线值。靶点网络分析确定了四种 microRNA 靶点中高度富集的 p53 信号通路和细胞周期基因。我们的研究结果表明细胞在转录后水平适应重力变化。根据我们的结果，我们建议细胞周期调节的变化作为太空任务中观察到的适应性变化的潜在解释。