Characterization of a novel microRNA, miR-188, elevated in serum of muscular dystrophy dog model

• Published in: PloS one 2019-01, Vol.14 (1), p.e0211597
• Main Authors: Shibasaki, Hiroyuki, Imamura, Michihiro, Arima, Sayuri, Tanihata, Jun, Kuraoka, Mutsuki, Matsuzaka, Yasunari, Uchiumi, Fumiaki, Tanuma, Sei-Ichi, Takeda, Shin'ichi
• Format: Article
• Language: English
• Subjects: Animal models; Animals; Antisense RNA; Biochemistry; Biological markers; Biology and Life Sciences; Biomarkers; Biomarkers - blood; Cell Differentiation; Cells, Cultured; Diagnosis; Differentiation; Disease Models, Animal; DNA microarrays; Dogs; Duchenne muscular dystrophy; Duchenne's muscular dystrophy; Dystrophy; Gene expression; Gene Expression Regulation; Gene regulation; Genes; Genetic aspects; Genetic regulation; Laboratory animals; Medicine and Health Sciences; Messenger RNA; Mice; MicroRNA; MicroRNAs; MicroRNAs - genetics; miRNA; Muscle, Skeletal - metabolism; Muscle, Skeletal - pathology; Muscles; Muscular dystrophy; Muscular Dystrophy, Animal - blood; Muscular Dystrophy, Animal - genetics; Muscular Dystrophy, Animal - pathology; Muscular Dystrophy, Duchenne - blood; Muscular Dystrophy, Duchenne - genetics; Muscular Dystrophy, Duchenne - pathology; Musculoskeletal system; Myoblasts - cytology; Myoblasts - metabolism; Myogenesis; Neurology; Neurosciences; Pharmaceutical sciences; Post-transcription; Psychiatry; Regeneration; Research and Analysis Methods; Ribonucleic acid; RNA; Skeletal muscle; Transcription (Genetics); Transcription factors
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0211597

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.