Let-7e-5p Regulates IGF2BP2, and Induces Muscle Atrophy

Let-7e-5p 调节 IGF2BP2 并诱导肌肉萎缩

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作者:Takuro Okamura, Hiroshi Okada, Yoshitaka Hashimoto, Saori Majima, Takafumi Senmaru, Naoko Nakanishi, Mai Asano, Masahiro Yamazaki, Masahide Hamaguchi, Michiaki Fukui

Aims

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.

Background and aims

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.

Conclusions

Based on our study, serum level of let-7e-5p may be used as a potential diagnostic marker for muscle atrophy.

Methods

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.

Results

We 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. Conclusions: Based on our study, serum level of let-7e-5p may be used as a potential diagnostic marker for muscle atrophy.

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