MicroRNA-351 inhibits denervation-induced muscle atrophy by targeting TRAF6
MicroRNA-351 inhibits denervation-induced muscle atrophy by targeting TRAF6
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MicroRNA-351 通过靶向 TRAF6 抑制去神经诱导的肌肉萎缩
DOI：
10.3892/etm.2016.3856
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发表时间：
2016-12-01
影响因子：
2.7
通讯作者：
Sun, Hualin
中科院分区：
文献类型：
--
作者：
He, Qianru;Qiu, Haying;Sun, Hualin
已经观察到MicroRNAs （miRs）参与各种生理病理过程的调节。然而，mirna对肌肉萎缩的影响尚未得到充分研究。在本研究中，结果表明miR-351在坐骨神经横断后的不同时间在胫骨前肌（TA）中存在差异表达，并且miR-351在mRNA和蛋白水平上的时间依赖性表达谱与肿瘤坏死因子受体相关因子6 （TRAF6）的表达谱呈负相关。双荧光素酶报告基因实验表明，miR-351能够通过直接靶向TRAF6的3'-非翻译区，显著下调TRAF6的表达水平。过表达miR-351抑制坐骨神经横断后TA肌湿重比或横截面积的显著下降。Western blot分析显示，过表达miR-351可抑制去神经TA肌中TRAF6、肌环指蛋白1 （MuRF1）和肌萎缩F-box （MAFBx）蛋白的表达水平。这些结果表明，miR-351至少部分通过负调控TRAF6以及TRAF6的两个下游信号分子MuRF1和MAFBx抑制坐骨神经横断后去神经支配诱导的TA肌萎缩。
MicroRNAs (miRs) have been observed to be involved in the modulation of various physiopathological processes. However, the impacts of miRNAs on muscle atrophy have not been fully investigated. In the present study, the results demonstrated that miR-351 was differentially expressed in the tibialis anterior (TA) muscle at various times following sciatic nerve transection, and the time-dependent expression profile of miR-351 was inversely correlated with that of tumor necrosis factor receptor-associated factor 6 (TRAF6) at the mRNA and protein levels. The dual luciferase reporter assay indicated that miR-351 was able to significantly downregulate the expression levels of TRAF6 by directly targeting the 3'-untranslated region of TRAF6. Overexpression of miR-351 inhibited a significant decrease in the wet weight ratio or cross-sectional area of the TA muscle following sciatic nerve transection. Western blot analysis indicated that the protein expression levels of TRAF6, muscle ring-finger protein 1 (MuRF1) and muscle atrophy F-box (MAFBx) in denervated TA muscles were suppressed by overexpression of miR-351. These results demonstrate that miR-351 inhibits denervation-induced atrophy of TA muscles following sciatic nerve transection at least partially through negative regulation of TRAF6 as well as MuRF1 and MAFBx, the two downstream signaling molecules of TRAF6.