Abstract
Background and AimsTo 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.MethodsTo 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.ResultsWe found that the expression of the miRNA, lethal (let)-7e-5p was significantly lower in ORX mice than that in Sham mice (p = 0.027); however, let-7e-5p 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 Igf2bp2 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 Igf2bp2 in myotube cells and inhibits the growth of the myosin heavy chain.ConclusionsBased on our study, serum level of let-7e-5p may be used as a potential diagnostic marker for muscle atrophy.
Highlights
Sarcopenia, an aging-related condition characterized by the loss of muscle mass, strength, and function, is an important global health concern [1]
We previously reported that activation of the Akt-mTOR pathway, caused by miR-23b-3p overexpression-mediated PTEN repression, counteracts skeletal muscle atrophy and has beneficial effects on the skeletal muscles, including increased expression of myosin heavy chain, myoD, and myogenin, and increased glucose uptake and ATP activity [15]
We examined the changes in Micro RNAs (miRNAs) expression in the soleus muscle of ORX mice by performing microarray analysis comparing the Sham and ORX mice administered with androgen (ORX+A)
Summary
Sarcopenia, an aging-related condition characterized by the loss of muscle mass, strength, and function, is an important global health concern [1]. Sarcopenia-associated muscular atrophy impairs motor function, and increases the likelihood of falls and fractures, affects daily activities [2, 3], and increases the risk of mortality [4]. The exact mechanism is unknown, reduced androgen production has been implicated in the pathogenesis of skeletal muscle atrophy. Roy et al reported an association between serum androgen concentration and skeletal muscle mass and. Let-7e-5p and Muscle Atrophy strength [6]. There is an urgent need to develop new therapeutic options to prevent androgen deficiency-induced skeletal muscle atrophy. 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
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
