He Qianru, Qiu Jiaying, Dai Ming, Fang Qingqing, Sun Xiaoqing, Gong Yanpei, Ding Fei, Sun Hualin
Jiangsu Key Laboratory of Neuroregeneration, Co-Innovation Center of Neuroregeneration, Nantong University, Nantong, Jiangsu 226001, P.R. China.
Department of Medical Laboratory, School of Public Health, Nantong University, Nantong, Jiangsu 226001, P.R. China.
Exp Ther Med. 2016 Dec;12(6):4029-4034. doi: 10.3892/etm.2016.3856. Epub 2016 Nov 2.
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.
已观察到微小RNA（miR）参与多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，坐骨神经横断后不同时间，miR-351在胫前肌（TA）中差异表达，且miR-351的时间依赖性表达谱在mRNA和蛋白质水平上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检测表明，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。miR-351过表达抑制了坐骨神经横断后TA肌肉湿重比或横截面积的显著降低。蛋白质印迹分析表明，miR-351过表达抑制了失神经支配的TA肌肉中TRAF6、肌肉环形指蛋白1（MuRF1）和肌肉萎缩F盒蛋白（MAFBx）的蛋白表达水平。这些结果表明，miR-351至少部分通过对TRAF6以及TRAF6的两个下游信号分子MuRF1和MAFBx的负调控，抑制坐骨神经横断后TA肌肉的失神经支配诱导的萎缩。
