MicroRNA-27b Regulates Mitochondria Biogenesis in Myocytes.
MicroRNA-27b Regulates Mitochondria Biogenesis in Myocytes.
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DOI：
10.1371/journal.pone.0148532
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发表时间：
2016
期刊：
影响因子：
3.7
通讯作者：
Zhu L
中科院分区：
文献类型：
--
作者：
Shen L;Chen L;Zhang S;Du J;Bai L;Zhang Y;Jiang Y;Li X;Wang J;Zhu L
MicroRNA (miRNA) 是一种小型非编码 RNA，影响多种生物途径的转录后调节。迄今为止，尚不完全了解 miRNA 如何调节线粒体生物发生。本研究旨在鉴定 miRNA-27b 在线粒体生物发生中的作用。 C2C12细胞中的线粒体含量在肌原性分化过程中显着增加，并伴随着miRNA-27b表达的显着降低。此外，预测的 miRNA-27b 靶基因叉头盒 j3 (Foxj3) 的表达在肌原性分化过程中也有所增加。荧光素酶活性测定证实 miRNA-27b 直接靶向 Foxj3 的 3'-非翻译区 (3'-UTR)。 miRNA-27b 的过度表达引起线粒体含量的减少以及相关线粒体基因和 Foxj3 在 mRNA 和蛋白质水平上的表达减少。当 miRNA-27b 过表达时，C2C12 细胞中 Foxj3 下游基因（例如 Mef2c、PGC1α、NRF1 和 mtTFA）的表达水平也降低。这些结果表明，miRNA-27b 可能通过在心肌细胞分化过程中下调 Foxj3 来影响线粒体生物发生。
MicroRNAs (miRNAs) are small, non-coding RNAs that affect the post-transcriptional regulation of various biological pathways. To date, it is not fully understood how miRNAs regulate mitochondrial biogenesis. This study aimed at the identification of the role of miRNA-27b in mitochondria biogenesis. The mitochondria content in C2C12 cells was significantly increased during myogenic differentiation and accompanied by a marked decrease of miRNA-27b expression. Furthermore, the expression of the predicted target gene of miRNA-27b, forkhead box j3 (Foxj3), was also increased during myogenic differentiation. Luciferase activity assays confirmed that miRNA-27b directly targets the 3’-untranslated region (3’-UTR) of Foxj3. Overexpression of miRNA-27b provoked a decrease of mitochondria content and diminished expression of related mitochondrial genes and Foxj3 both at mRNA and protein levels. The expression levels of downstream genes of Foxj3, such as Mef2c, PGC1α, NRF1 and mtTFA, were also decreased in C2C12 cells upon overexpression of miRNA-27b. These results suggested that miRNA-27b may affect mitochondria biogenesis by down-regulation of Foxj3 during myocyte differentiation.