Iguchi Haruhisa, Kosaka Nobuyoshi, Ochiya Takahiro
Section for Studies on Metastasis; National Cancer Center Research Institute; Chuo-ku, Tokyo Japan.
Commun Integr Biol. 2010 Sep;3(5):478-81. doi: 10.4161/cib.3.5.12693.
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.
微小RNA（miRNA）的生理作用被广泛认为是一种微调器，可在转录后调节起源细胞中多个基因的表达。在此，我们强调miRNA的两个重要特征：（1）它们从产生细胞中分泌出来；（2）它们能够在体外和体内的活细胞之间传递基因沉默信号。我们发现miRNA的释放是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的，这一发现为miRNA在人体体液中的循环提供了合理的解释。这一发现有助于将循环miRNA开发为多种疾病的诊断生物标志物。我们还证明，分泌型miR-16被转移到皮下接种于裸鼠的前列腺癌PC-3M细胞中，导致其靶基因受到抑制。这一结果表明，分泌型miRNA与其主要作用一致，也可以在受体细胞中作为翻译抑制剂发挥作用。总之，miRNA从其初始细胞中释放出来，从而能够作为基因表达的沉默主宰发挥其全部潜能。
