Skeletal muscle specific overexpression of miRNA-1 impairs mechanical overload-induced skeletal muscle hypertrophy [RNA-Seq]. Skeletal muscle specific overexpression of miRNA-1 impairs mechanical overload-induced skeletal muscle hypertrophy [RNA-Seq]

MicroRNAs (miRNAs) are small, non-coding RNAs that play a critical role in regulating gene expression post-transcriptionally. Skeletal muscle-specific miRNAs, including miR-1, are important for skeletal muscle development and maintenance. In response to mechanical loading, skeletal muscle levels of miR-1 decrease by approximately 50%, suggesting a potential involvement in muscle hypertrophy. In the current investigation, we hypothesized that a reduction of miR-1 levels in response to mechanical loading would be necessary for skeletal muscle growth to occur. By significantly elevating miR-1 levels during the hypertrophic process via lentiviral delivery, we observed a blunted growth response in the plantaris muscle subjected to synergist ablation. A deeper RNA-based integrative analysis (transcriptomics and RNA eCLIP) indicates that miR-1 inhibits the expression of Itm2a and Melusin, two membrane-related proteins. While their exact mechanism in muscle hypertrophy is yet to be identified, our results suggest that miR-1-regulated membrane proteins are important for skeletal muscle hypertrophy. Overall design: To explore the role of miR-1 in skeletal muscle, we overexpressed miR-1 (lentivirus injection) in mice (Mimic group) that underwent 10 days of MOV-induced muscle hypertrophy. We then perform the gene expression analysis using data from RNA-seq

微小核糖核酸（MicroRNAs，miRNAs）是一类小型非编码RNA，在转录后基因表达调控中发挥关键作用。骨骼肌特异性miRNAs（含miR-1）对骨骼肌的发育与稳态维持至关重要。当受到机械负荷刺激时，骨骼肌内miR-1的表达水平可下降约50%，提示其可能参与肌肉肥大过程。本研究中，我们提出假说：机械负荷诱导的miR-1水平下调，是骨骼肌生长发生的必要条件。通过慢病毒递送在肌肉肥大进程中显著升高miR-1的表达水平后，我们观察到接受协同肌切除术处理的跖肌，其生长反应受到明显抑制。进一步的RNA整合组学分析（转录组学与RNA增强型交联免疫沉淀（RNA eCLIP））结果显示，miR-1可抑制两种膜相关蛋白Itm2a与Melusin的表达。尽管这两种蛋白在肌肉肥大中的具体作用机制尚未阐明，但我们的研究结果表明，受miR-1调控的膜相关蛋白对骨骼肌肥大过程具有重要意义。实验整体设计：为探究miR-1在骨骼肌中的作用，我们对接受10天MOV诱导肌肉肥大的小鼠，通过慢病毒注射方式过表达miR-1，设为模拟物组（Mimic group）；随后利用RNA-seq数据开展基因表达分析。