Lamon Séverine, Zacharewicz Evelyn, Butchart Lauren C, Orellana Liliana, Mikovic Jasmine, Grounds Miranda D, Russell Aaron P
Deakin University, School of Exercise and Nutrition Sciences, Institute for Physical Activity and Nutrition (I-PAN), Geelong, Australia.
The University of Western Australia, School of Anatomy, Physiology and Human Biology, Perth, WA, Australia.
BMC Genomics. 2017 Jan 7;18(1):52. doi: 10.1186/s12864-016-3399-2.
MiRNAs are essential regulators of skeletal muscle development and homeostasis. To date, the role and regulation of miRNAs in myogenesis have been mostly studied in tissue culture and during embryogenesis. However, little information relating to miRNA regulation during early post-natal skeletal muscle growth in mammals is available. Using a high-throughput miRNA qPCR-based array, followed by stringent statistical and bioinformatics analysis, we describe the expression pattern and putative role of 768 miRNAs in the quadriceps muscle of mice aged 2 days, 2 weeks, 4 weeks and 12 weeks.
Forty-six percent of all measured miRNAs were expressed in mouse quadriceps muscle during the first 12 weeks of life. We report unprecedented changes in miRNA expression levels over time. The expression of a majority of miRNAs significantly decreased with post-natal muscle maturation in vivo. MiRNA clustering identified 2 subsets of miRNAs that are potentially involved in cell proliferation and differentiation, mainly via the regulation of non-muscle specific targets.
Collective miRNA expression in mouse quadriceps muscle is subjected to substantial levels of regulation during the first 12 weeks of age. This study identified a new suite of highly conserved miRNAs that are predicted to influence early muscle development. As such it provides novel knowledge pertaining to post-natal myogenesis and muscle regeneration in mammals.
微小RNA(miRNA)是骨骼肌发育和体内平衡的重要调节因子。迄今为止,miRNA在肌生成中的作用和调控主要是在组织培养和胚胎发育过程中进行研究的。然而,关于哺乳动物出生后早期骨骼肌生长过程中miRNA调控的信息却很少。我们利用基于高通量miRNA定量PCR的芯片,随后进行严格的统计和生物信息学分析,描述了768种miRNA在2天、2周、4周和12周龄小鼠股四头肌中的表达模式及假定作用。
在小鼠出生后的前12周内,所有检测的miRNA中有46%在股四头肌中表达。我们报道了miRNA表达水平随时间出现的前所未有的变化。在体内,随着出生后肌肉成熟,大多数miRNA的表达显著下降。miRNA聚类分析确定了2个miRNA亚群,它们可能主要通过调控非肌肉特异性靶标参与细胞增殖和分化。
在出生后的前12周内,小鼠股四头肌中的miRNA集体表达受到大量调控。本研究鉴定出一组新的高度保守的miRNA,预计它们会影响早期肌肉发育。因此,该研究提供了有关哺乳动物出生后肌生成和肌肉再生的新知识。