Department of Endocrinology and Metabolism, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan.
Department of Diabetes and Endocrinology, Matsushita Memorial Hospital, Moriguchi, Japan.
Front Endocrinol (Lausanne). 2021 Dec 24;12:791363. doi: 10.3389/fendo.2021.791363. eCollection 2021.
To understand the role of microRNAs in muscle atrophy caused by androgen-depletion, we performed microarray analysis of microRNA expression in the skeletal muscles of Sham, orchiectomized (ORX), and androgen-treated ORX mice.
To clarify role and mechanisms of let-7e-5p in the muscle, the effect of let-7e-5p overexpression or knockdown on the expression of myosin heavy chain, glucose uptake, and mitochondrial function was investigated in C2C12 myotube cells. Moreover, we examined serum let-7e-5p levels among male subjects with type 2 diabetes.
We found that the expression of the miRNA, lethal was significantly lower in ORX mice than that in Sham mice (p = 0.027); however, expression in androgen-treated ORX mice was higher (p = 0.047). Suppression of let-7e-5p significantly upregulated the expression of myosin heavy chain, glucose uptake, and mitochondrial function. Real-time PCR revealed a possible regulation involving let-7e-5p and mRNA and protein in C2C12 cells. The serum let-7e-5p levels were significantly lower, which might be in compensation, in subjects with decreased muscle mass compared to subjects without decreased muscle mass. Let-7e-5p downregulates the expression of in myotube cells and inhibits the growth of the myosin heavy chain.
Based on our study, serum level of let-7e-5p may be used as a potential diagnostic marker for muscle atrophy.
为了了解雄激素耗竭引起的肌肉萎缩中 microRNAs 的作用，我们对假手术、去势（ORX）和雄激素处理的 ORX 小鼠骨骼肌中的 microRNA 表达进行了 microarray 分析。
为了阐明 let-7e-5p 在肌肉中的作用和机制，我们在 C2C12 肌管细胞中研究了 let-7e-5p 过表达或敲低对肌球蛋白重链、葡萄糖摄取和线粒体功能表达的影响。此外，我们还检测了 2 型糖尿病男性患者的血清 let-7e-5p 水平。
我们发现 miRNA 致死的表达在 ORX 小鼠中明显低于 Sham 小鼠（p = 0.027）；然而，雄激素处理的 ORX 小鼠中的表达更高（p = 0.047）。抑制 let-7e-5p 可显著上调肌球蛋白重链、葡萄糖摄取和线粒体功能的表达。实时 PCR 显示 C2C12 细胞中可能存在 let-7e-5p 和 mRNA 和蛋白的调节。与肌肉量未减少的受试者相比，肌肉量减少的受试者血清 let-7e-5p 水平明显降低，可能是代偿性的。let-7e-5p 在肌管细胞中下调 的表达并抑制肌球蛋白重链的生长。
根据我们的研究，血清 let-7e-5p 水平可作为肌肉萎缩的潜在诊断标志物。
