Transcriptome-derived evidence reveals the regulatory network in the skeletal muscle of the fast-growth mstnb^-/- male tilapia

Myostatin (Mstn) negatively regulates muscle growth and Mstn deficiency induced "double-skeletal muscle" development in vertebrates, including tilapias. In this study, we performed a transcriptomic analysis of skeletal muscle from both wild-type and mstnb^-/- males to investigate the molecular mechanisms underlying skeletal muscle hypertrophy in mstnb^-/- mutants. We identified 4697 differentially expressed genes (DEGs), 113 differentially expressed long non-coding RNAs (DE lncRNAs), 211 differentially expressed circular RNAs (DE circRNAs), and 98 differentially expressed microRNAs (DE miRNAs). The DEGs were significantly enriched in proteasome and ubiquitin-mediated proteolysis pathways. Cis- and trans-targeting genes of DE lncRNAs were also notably enriched in the above two pathways. The putative host genes of DE circRNAs linked to myofibrils, contractile fibers, and so on. Additionally, DE miRNAs were associated with ubiquitin-mediated proteolysis and key signaling pathways, including AMPK, FoxO, and mTOR. Furthermore, the core competing endogenous RNA (ceRNA) network was constructed comprising 31 DEGs, 37 DE miRNAs, 14 DE circRNAs, and 45 DE lncRNAs. The key roles of ubiquitin-proteasome system were highlighted in the ceRNA network. Taken together, this study provides a novel perspective on muscle mass increase in Mstn mutants through the repression of protein degradation and facilitates our understanding of the molecular mechanisms of skeletal muscle hypertrophy in fish.