Secretory microRNAs as a versatile communication tool.
Secretory microRNAs as a versatile communication tool.
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DOI：
10.4161/cib.3.5.12693
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发表时间：
2010-09-01
影响因子：
--
通讯作者：
Ochiya, Takahiro
中科院分区：
文献类型：
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作者：
Iguchi, Haruhisa;Kosaka, Nobuyoshi;Ochiya, Takahiro
microRNA（miRNAs）的生理作用被广泛认为是转录后调节起源细胞中多个基因表达的微调器。在这里，我们强调了miRNAs的两个重要特征：（1）它们从生产细胞中分泌出来，（2）它们可以在体外和体内活细胞之间传递基因沉默信号。通过我们的发现，miRNA的释放通过与外泌体分泌相关的神经酰胺依赖性机制被主动控制，可以为人类体液中miRNA的循环提供合乎逻辑的解释。这一发现有助于开发循环miRNA作为各种疾病的诊断生物标志物。我们还证明了分泌型miR-16被转移到裸鼠皮下移植的前列腺癌PC-3 M细胞中，导致其靶基因的抑制。这一结果表明，忠实于它们的主要作用，分泌型miRNA也可以在受体细胞中作为翻译抑制剂发挥作用。总之，miRNAs从其初始细胞中释放出来，从而它们可以发挥其作为基因表达沉默大师的全部潜力。
The physiological role of microRNAs (miRNAs) is widely appreciated as a fine-tuner to post-transcriptionally regulate the expression of multiple genes in the cells of origin. Here, we highlight two significant characteristics of miRNAs: (1) they are secreted from the producing cells and (2) they can deliver the gene silencing signals between living cells in vitro and in vivo. The circulation of miRNAs in human body fluids can be provided with a logical explanation by our discovery that the release of miRNAs is actively controlled through a ceramide-dependent machinery associated with exosome secretion. This finding can contribute to the development of circulating miRNAs as diagnostic biomarkers for a variety of diseases. We also demonstrated that secretory miR-16 was transferred into prostate cancer PC-3M cells subcutaneously xenografted in nude mice, resulting in the suppression of its target gene. This result suggests that faithfully to their primary role, secretory miRNAs can function as a translational inhibitor in recipient cells as well. In conclusion, miRNAs are liberated from their incipient cells, whereby they can exert their full potentials as a silence master of gene expressions.