Department of Molecular Therapy, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Kodaira, Tokyo, Japan.
Department of Gene Regulation, Faculty of Pharmaceutical Sciences, Tokyo University of Science, Noda, Chiba, Japan.
PLoS One. 2019 Jan 30;14(1):e0211597. doi: 10.1371/journal.pone.0211597. eCollection 2019.
MicroRNAs (miRNAs) are non-coding small RNAs that regulate gene expression at the post-transcriptional level. Several miRNAs are exclusively expressed in skeletal muscle and participate in the regulation of muscle differentiation by interacting with myogenic factors. These miRNAs can be found at high levels in the serum of patients and animal models for Duchenne muscular dystrophy, which is expected to be useful as biomarkers for their clinical conditions. By miRNA microarray analysis, we identified miR-188 as a novel miRNA that is elevated in the serum of the muscular dystrophy dog model, CXMDJ. miR-188 was not muscle-specific miRNA, but its expression was up-regulated in skeletal muscles associated with muscle regeneration induced by cardiotoxin-injection in normal dogs and mice. Manipulation of miR-188 expression using antisense oligo and mimic oligo RNAs alters the mRNA expression of the myogenic regulatory factors, MRF4 and MEF2C. Our results suggest that miR-188 is a new player that participates in the gene regulation process of muscle differentiation and that it may serve as a serum biomarker reflecting skeletal muscle regeneration.
微小 RNA（miRNAs）是一类非编码的小 RNA，通过与肌源性因子相互作用，在转录后水平调控基因表达。一些 miRNAs 仅在骨骼肌中表达，并参与肌肉分化的调控。这些 miRNAs 在杜氏肌营养不良症（Duchenne muscular dystrophy）患者和动物模型的血清中含量较高，有望成为其临床状况的生物标志物。通过 miRNA 微阵列分析，我们鉴定出 miR-188 是一种在肌肉营养不良犬模型 CXMDJ 血清中升高的新型 miRNA。miR-188 不是肌肉特异性 miRNA，但在正常犬和小鼠中，它在心肌毒素注射诱导的肌肉再生相关的骨骼肌中表达上调。使用反义寡核苷酸和模拟寡核苷酸 RNA 对 miR-188 表达进行操作，改变了肌源性调节因子 MRF4 和 MEF2C 的 mRNA 表达。我们的结果表明，miR-188 是参与肌肉分化基因调控过程的新成员，可能作为反映骨骼肌再生的血清生物标志物。
