Effects of Simulated Microgravity on Expression Profile of MicroRNA in Human Lymphoblastoid Cells

Effects of Simulated Microgravity on Expression Profile of MicroRNA in Human Lymphoblastoid Cells
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DOI:
10.1074/jbc.m111.267765
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发表时间:
2011-09-16
影响因子:
4.8
通讯作者:
Wu, Honglu
Wu, Honglu
中科院分区:
生物学2区
文献类型:
--
作者:
Mangala, Lingegowda S.;Zhang, Ye;Wu, Honglu

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本研究探讨了模拟微重力条件下microRNA(miRNA)及其相关基因表达的变化。与静止的1x g相比,微重力已被证明会改变培养细胞或动物的整体基因表达模式和蛋白质水平。miRNA最近成为基因表达的重要调节因子,可能调节多达三分之一的人类基因。然而,关于重力改变对miRNA表达的影响知之甚少。为了验证以下假设,即miRNA表达谱将在零重力下改变,从而导致基因表达的调节改变,从而导致细胞中的代谢或功能变化,我们在高纵横比容器(生物反应器)中培养TK 6人淋巴母细胞72小时,无论是在旋转条件下模拟太空中的微重力还是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-34 a、miR-423- 5 p、miR-22、miR-141、miR-618和miR-222。为了证实这种改变的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,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EGR 2、ETS 1和c-REL在内的几种转录因子的表达发生了改变。总之,本文报道的结果表明,模拟微重力改变了TK 6细胞中miRNA和基因的表达。据我们所知,这项研究是首次报道模拟微重力对miRNA和相关基因表达的影响。
This study explores the changes in expression of microRNA (miRNA) and related genes under simulated microgravity conditions. In comparison with static 1 x 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 miR150, 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.