Abstract
There is growing evidence that non-coding RNAs are emerging as critical regulators of skeletal muscle development. In order to reveal their functional roles and regulatory mechanisms, we constructed a lncRNA–miRNA–mRNA network according to the ceRNA (competitive endogenous RNA) theory, using our high-throughput sequencing data. Subsequently, the network analysis, GO (Gene Ontology) analysis, and KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway analysis were performed for functional annotation and exploration of lncRNA ceRNAs. The results uncovered a scale-free characteristics network which exhibited high functional specificity for bovine skeletal muscle development: co-expression lncRNAs were significantly enriched in muscle development related biological processes and the Wnt signaling pathway. Furthermore, GSEA (Gene Set Enrichment Analysis) indicated that the risk score has a tendency to associate with myogenesis, and differentially expressed RNAs were validated by qPCR, further confirming the credibility of our network. In summary, this study provides insights into lncRNA-mediated ceRNA function and mechanisms in bovine skeletal muscle development and will expand our understanding of lncRNA biology in mammals.
Highlights
Vertebrates’ skeletal muscles are mostly derived from paraxial mesodermal somites and undergo hyperplasia and hypertrophy process successively (Buckingham et al, 2003; Guo et al, 2015)
The scale-free distribution and module characteristics of the entire network implied the presence of functionally important nodes in bovine skeletal muscle development
BP terms like muscle cell cellular homeostasis, mesoderm development, axis specification, and dorsal/ventral pattern formation were found in the enrichments, indicating the regulatory roles of these co-expression lncRNAs in bovine skeletal muscle development (Figure 4A)
Summary
Vertebrates’ skeletal muscles are mostly derived from paraxial mesodermal somites and undergo hyperplasia and hypertrophy process successively (Buckingham et al, 2003; Guo et al, 2015). Several studies showed that post-transcriptional regulation has a significant effect on skeletal muscle development (Cesana et al, 2011). Accumulating evidence has suggested that ncRNAs like miRNA (microRNA) and lncRNA (long non-coding RNA) are emerging as critical regulators of skeletal muscle development (Williams et al, 2009; Matsumoto et al, 2017). Like mRNA-like transcripts longer than 200 nucleotides, lncRNAs have extremely abundant binding sites for microRNAs (Phelps et al, 2016), and LncRNAs such as linc-MD1 (Cesana et al, 2011), H19 (Kallen et al, 2013), lncMyoD (Gong et al, 2015) and lncmg (Zhu et al, 2017) showed relevant roles in myogenesis by acting as ceRNA (competing endogenous RNA). The aim of this study was to further identify a novel regulatory mechanism based on the ceRNA theory in bovine skeletal muscle development
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