MiR-23-TrxR1 as a novel molecular axis in skeletal muscle differentiation.
MiR-23-TrxR1 as a novel molecular axis in skeletal muscle differentiation.
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DOI：
10.1038/s41598-017-07575-0
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发表时间：
2017-08-03
影响因子：
4.6
通讯作者：
Caporossi D
中科院分区：
文献类型：
--
作者：
Mercatelli N;Fittipaldi S;De Paola E;Dimauro I;Paronetto MP;Jackson MJ;Caporossi D
硫氧还蛋白还原酶1（TrxR 1）是一种含硒半胱氨酸的蛋白质，参与细胞氧化还原稳态，在骨骼肌分化中下调。在这里，我们表明，TrxR 1减少发生在肌肉发生功能参与协调这一细胞过程。事实上，TrxR 1缺失通过诱导早期肌生成相关基因表达模式（包括肌生成素和Myf 5上调以及细胞周期蛋白D1减少）来减少成肌细胞生长。相反，在分化过程中TrxR 1的过表达通过负面影响Myogenin和MyHC的表达来延迟肌生成过程。此外，我们发现miR-23 a和miR-23 b在C2 C12分化早期表达增加，它们通过直接结合TrxR 1 mRNA的3′ UTR参与TrxR 1表达的调节。有趣的是，C2 C12分化期间对miR-23 a和miR-23 b的强制抑制部分挽救了TrxR 1水平并延迟了肌源性标志物的表达，这表明miR-23通过TrxR 1抑制参与了肌生成。总之，我们的研究结果首次描述了一种新的分子轴，它通过miR-23调节TrxR 1在骨骼肌分化中起作用。
Thioredoxin reductase 1 (TrxR1) is a selenocysteine-containing protein involved in cellular redox homeostasis which is downregulated in skeletal muscle differentiation. Here we show that TrxR1 decrease occurring during myogenesis is functionally involved in the coordination of this cellular process. Indeed, TrxR1 depletion reduces myoblasts growth by inducing an early myogenesis -related gene expression pattern which includes myogenin and Myf5 up-regulation and Cyclin D1 decrease. On the contrary, the overexpression of TrxR1 during differentiation delays myogenic process, by negatively affecting the expression of Myogenin and MyHC. Moreover, we found that miR-23a and miR-23b - whose expression was increased in the early stage of C2C12 differentiation - are involved in the regulation of TrxR1 expression through their direct binding to the 3′ UTR of TrxR1 mRNA. Interestingly, the forced inhibition of miR-23a and miR-23b during C2C12 differentiation partially rescues TrxR1 levels and delays the expression of myogenic markers, suggesting the involvement of miR-23 in myogenesis via TrxR1 repression. Taken together, our results depict for the first time a novel molecular axis, which functionally acts in skeletal muscle differentiation through the modulation of TrxR1 by miR-23.
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影响因子：
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作者：
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