Comprehensive miRNA Profiling of Skeletal Muscle and Serum in Induced and Normal Mouse Muscle Atrophy During Aging

Abstract

Age-associated loss of muscle mass and function is a major cause of morbidity and mortality in the elderly adults. Muscular atrophy can also be induced by disuse associated with long-term bed rest or disease. Although miRNAs regulate muscle growth, regeneration, and aging, their potential role in acute muscle atrophy is poorly understood. Furthermore, alterations in circulating miRNA levels have been shown to occur during aging but their potential as noninvasive biomarkers for muscle atrophy remains largely unexplored. Here, we report comprehensive miRNA expression profiles by miRNA-seq analysis in tibialis anterior muscle and serum of a disuse-induced atrophy mouse model, mimicking the acute atrophy following long-term bed rest, as compared to those of young and old mice. Comparative analysis and validation studies have revealed that miR-455-3p was significantly decreased in muscle of both induced-atrophy model and old mice, whereas miR-434-3p was decreased in both serum and muscle of old mice, as compared to young mice. Furthermore, upregulation of miR-455-3p in fully differentiated C2C12 myoblasts induced a hypertrophic phenotype. These results suggest that deregulation of miR-455-3p may play a functional role in muscle atrophy and miR-434-3p could be a candidate serum biomarker of muscle aging.

A subset of microRNAs in the Dlk1‐Dio3 cluster regulates age‐associated muscle atrophy by targeting Atrogin‐1

“…On the basis of our previous reports showing the down-regulation of the Dlk1-Dio3 cluster of miRNAs in muscle aging, [15][16][17] we investigated the possibility that the miRNAs in the cluster could regulate muscle hypertrophy or atrophy. Therefore, we examined whether 42 pre-miRNAs, conserved in both mouse and human sequences, in the Dlk1-Dio3 locus are involved in the regulation of atrophy, a major phenotype of aged muscle.…”

“…[10][11][12][13][14] We recently demonstrated that >50% of down-regulated miRNAs in aged mouse skeletal muscle and myoblasts are clustered in the delta-like homologue 1 and the type III iodothyronine deiodinase (Dlk1-Dio3) imprinted genomic region. [15][16][17] Dlk1-Dio3 is the largest known placental mammalian-specific miRNA cluster. The majority of miRNAs are contained within the antisense Rtl1 and the larger transcript of Mirg.…”

Chronic vitamin D insufficiency impairs physical performance in C57BL/6J mice

“…Of these 4.8 ± 1.0 x 10 5 and 4.9 ± 1.2 x 10 5 reads for each STD and LOW, respectively, were mapped to known miRNAs using mIRBase v21. To avoid using insufficient data due to low expression, we removed any miRNA that did not reach at least 10 reads across 66% or more of the samples (per Jung et al [ 32 ]), yielding a total of 202 unique miRNAs for further analysis. Our data revealed 12 miRNAs with potential for differential expression between STD and LOW ( Figure 6 and Table 2 , p<0.05); however, after false discovery rate correction we identified only one differentially expressed miRNA, mIR26a-5p, with a q‑value = 0.0392.…”

MicroRNA‑34a inhibits bladder cancer cell migration and invasion, and upregulates PTEN expression

“…In the present study, downregulation of miR-34a in bladder biopsies and plasma may be used to effectively distinguish between patients with bladder cancer and the healthy controls. miR-34a expression levels were not significantly associated with age, sex, smoking or drinking habits, which are considered influencing factors on the expression levels of certain miRNAs (20)(21)(22). Therefore, miR-34a may serve as a reliable biomarker for the detection of bladder cancer.…”