Radiation Biophysics Laboratory, NASA Johnson Space Center, Houston, TX 77058, USA.
J Biol Chem. 2011 Sep 16;286(37):32483-90. doi: 10.1074/jbc.M111.267765. Epub 2011 Jul 20.
This study explores the changes in expression of microRNA (miRNA) and related genes under simulated microgravity conditions. In comparison with static 1 × g, microgravity has been shown to alter global gene expression patterns and protein levels in cultured cells or animals. miRNA has recently emerged as an important regulator of gene expression, possibly regulating as many as one-third of all human genes. However, very little is known about the effect of altered gravity on miRNA expression. To test the hypothesis that the miRNA expression profile would be altered in zero gravity resulting in altered regulation of gene expression leading to metabolic or functional changes in cells, we cultured TK6 human lymphoblastoid cells in a high aspect ratio vessel (bioreactor) for 72 h either in the rotating condition to model microgravity in space or in the static condition as a control. Expression of several miRNAs was changed significantly in the simulated microgravity condition including miR-150, miR-34a, miR-423-5p, miR-22, miR-141, miR-618, and miR-222. To confirm whether this altered miRNA expression correlates with gene expression and functional changes of the cells, we performed DNA microarray and validated the related genes using quantitative RT-PCR. Expression of several transcription factors including EGR2, ETS1, and c-REL was altered in simulated microgravity conditions. Taken together, the results reported here indicate that simulated microgravity alters the expression of miRNAs and genes in TK6 cells. To our knowledge, this study is the first to report the effects of simulated microgravity on the expression of miRNA and related genes.
本研究探讨了模拟微重力条件下 microRNA（miRNA）和相关基因表达的变化。与静态 1×g 相比，微重力已被证明会改变培养细胞或动物中的全局基因表达模式和蛋白质水平。miRNA 最近作为基因表达的重要调节剂而出现，可能调节多达三分之一的人类基因。然而，对于重力变化对 miRNA 表达的影响知之甚少。为了验证以下假设，即微重力会改变 miRNA 表达谱，从而改变基因表达的调节，导致细胞代谢或功能发生变化，我们将 TK6 人淋巴母细胞系在高纵横比容器（生物反应器）中培养 72 小时，要么在旋转条件下模拟空间微重力，要么在静态条件下作为对照。在模拟微重力条件下，几种 miRNA 的表达发生了显著变化，包括 miR-150、miR-34a、miR-423-5p、miR-22、miR-141、miR-618 和 miR-222。为了确认这种改变的 miRNA 表达是否与细胞的基因表达和功能变化相关，我们进行了 DNA 微阵列分析，并使用定量 RT-PCR 验证了相关基因。在模拟微重力条件下，包括 EGR2、ETS1 和 c-REL 在内的几种转录因子的表达发生了改变。总之，这里报告的结果表明，模拟微重力改变了 TK6 细胞中 miRNA 和基因的表达。据我们所知，这项研究首次报道了模拟微重力对 miRNA 和相关基因表达的影响。
