Diversity and Differential Expression of MicroRNAs in the Human Skeletal Muscle with Distinct Fiber Type Composition

Abstract

The ratio of fast- and slow-twitch fibers in human skeletal muscle is variable and largely determined by genetic factors. In this study, we investigated the contribution of microRNA (miRNA) in skeletal muscle fiber type composition. The study involved biopsy samples of the vastus lateralis muscle from 24 male participants with distinct fiber type ratios. The miRNA study included samples from five endurance athletes and five power athletes with the predominance of slow-twitch (61.6–72.8%) and fast-twitch (69.3–80.7%) fibers, respectively. Total and small RNA were extracted from tissue samples. Total RNA sequencing (N = 24) revealed 352 differentially expressed genes between the groups with the predominance of fast- and slow-twitch muscle fibers. Small RNA sequencing showed upregulation of miR-206, miR-501-3p and miR-185-5p, and downregulation of miR-499a-5p and miR-208-5p in the group of power athletes with fast-twitch fiber predominance. Two miRtronic miRNAs, miR-208b-3p and miR-499a-5p, had strong correlations in expression with their host genes (MYH7 and MYH7B, respectively). Correlations between the expression of miRNAs and their experimentally validated messenger RNA (mRNA) targets were calculated, and 11 miRNA–mRNA interactions with strong negative correlations were identified. Two of them belonged to miR-208b-3p and miR-499a-5p, indicating their regulatory links with the expression of CDKN1A and FOXO4, respectively.