Department of Biomedical Engineering, Nanjing University of Aeronautics and Astronautics, Nanjing 211106, China.
Int J Mol Sci. 2020 Oct 14;21(20):7585. doi: 10.3390/ijms21207585.
Previous studies have demonstrated that microgravity could lead to health risks. The investigation of the molecular mechanisms from the aspect of systems biology has not been performed yet. Here, we integratively analyzed transcriptional and post-transcriptional regulations based on gene and miRNA expression profiles in human peripheral blood lymphocytes cultured in modeled microgravity. Two hundred and thirty dysregulated TF-miRNA (transcription factor and microRNA) feed-forward loops (FFLs) were identified in microgravity. The immune, cardiovascular, endocrine, nervous and skeletal system subnetworks were constructed according to the functions of dysregulated FFLs. Taking the skeletal system as an example, most of genes and miRNAs in the subnetwork were involved in bone loss. In addition, several drugs have been predicted to have potential to reduce bone loss, such as traditional Chinese medicines Emodin and Ginsenoside Rh2. Furthermore, we investigated the relationships between microgravity and 20 cancer types, and found that most of cancers might be promoted by microgravity. For example, rectum adenocarcinoma (READ) might be induced by microgravity through reducing antigen presentation and suppressing IgA-antibody-secreting cells' migration. Collectively, TF-miRNA FFL might provide a novel mechanism to elucidate the changes induced by microgravity, serve as drug targets to relieve microgravity effects, and give new insights to explore the relationships between microgravity and cancers.
先前的研究表明，微重力可能会带来健康风险。从系统生物学的角度研究其分子机制尚未进行。在这里，我们综合分析了在模拟微重力条件下培养的人外周血淋巴细胞的基因和 miRNA 表达谱的转录和转录后调控。在微重力条件下，确定了 230 个失调的 TF-miRNA（转录因子和 microRNA）前馈环（FFL）。根据失调 FFL 的功能构建了免疫、心血管、内分泌、神经和骨骼系统子网。以骨骼系统为例，子网中的大多数基因和 miRNA 都参与了骨丢失。此外，还预测了几种药物可能具有减轻骨丢失的潜力，如传统中药大黄素和人参皂苷 Rh2。此外，我们研究了微重力与 20 种癌症类型之间的关系，发现大多数癌症可能会受到微重力的促进。例如，微重力可能通过减少抗原呈递和抑制 IgA 抗体分泌细胞的迁移来诱导直肠腺癌（READ）。总的来说，TF-miRNA FFL 可能为阐明微重力诱导的变化提供了一种新的机制，可作为缓解微重力影响的药物靶点，并为探索微重力与癌症之间的关系提供新的见解。
