Abstract
The microRNA (miR)-17 family is widely expressed in mammalian tissues and play important roles in various physiological and pathological processes. Here, the functions of miR-106a-5p, a member of miR-17 family, were explored during myogenic differentiation in C2C12 cell line. First, miR-106a-5p was found to be relatively lower expressed in two-month skeletal muscle tissues and gradually decreased upon myogenic stimuli. Forced expression of miR-106a-5p significantly reduced the differentiation index, fusion index as well as the expression of myogenic markers (MyoD, MyoG, MyHC, Myomixer, Myomarker). Meanwhile, the levels of phosphorylated AKT were reduced by overexpression of miR-106a-5p, and administration of insulin-like growth factor 1 (IGF1), a booster of myogenic differentiation, could recover all the inhibitory effects above of miR-106a-5p. Furthermore, miR-106a-5p was elevated in aged muscles and dexamethasone (DEX)-treated myotubes, and up-regulation of miR-106a-5p significantly reduced the diameters of myotubes accompanied with increased levels of muscular atrophy genes and decreased PI3K/AKT activities. Finally, miR-106a-5p was demonstrated to directly bind to the 3’-UTR of PIK3R1, thus, repress the PI3K/AKT signaling.
Highlights
Skeletal muscle comprises approximately 50% of the body’s weight and is an endocrine and paracrine organ that plays a key role in the maintenance of the internal environment and homeostasis [1]
MiR-106a-5p was highly conserved among detected species based on the nucleotide sequences (Figure 1A)
MiR-106a-5p was widely expressed in various tissues in two-month mice, especially in heart and kidney, but a small amount of expression was detected in skeletal muscle (Figure 1B)
Summary
Skeletal muscle comprises approximately 50% of the body’s weight and is an endocrine and paracrine organ that plays a key role in the maintenance of the internal environment and homeostasis [1]. Myf, MyoD and MRF4 are myogenic determination factors, and Myogenin is a downstream effector of MyoD and MRF4, and activate the myogenic differentiation program [3,4]. It has been reported that many pathways are involved in myogenesis, such as Wnt/β-Catenin Signaling [5], the TGFβ signaling pathway [6,7], JAK/STAT signaling pathway [8], and PI3K/AKT signaling pathway [9,10]. More and more microRNAs (miRs) have been reported to participate in myogenesis, such as miR-127 [11], miR-133 [12], Genes 2018, 9, 333; doi:10.3390/genes9070333 www.mdpi.com/journal/genes miR-1/206 [13], and miR-432 [14]. There are still many miRs that remain to be discovered in myoblasts differentiation and muscle formation
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