circPTPN4 regulates myogenesis via the miR-499-3p/NAMPT axis.

Background: Circular RNAs (circRNAs) are a novel class of endogenous ncRNA, which widely exist in the transcriptomes of different species and tissues. Recent studies indicate important roles for circRNAs in the regulation of gene expression by acting as competing endogenous RNAs (ceRNAs). However, the specific role of circRNAs in myogenesis is still poorly understood. In this study, we attempted to systematically identify the circRNAs involved in myogenesis and analyze the biological functions of circRNAs in chicken skeletal muscle development.

Results: In total, 532 circRNAs were identified as being differentially expressed between pectoralis major (PEM) and soleus (SOL) in 7-week-old Xinghua chicken. Among them, a novel circRNA (novel_circ_002621), generated by PTPN4 gene, was named circPTPN4 and identified. circPTPN4 is highly expressed in skeletal muscle, and its expression level is upregulated during myoblast differentiation. circPTPN4 facilitates the proliferation and differentiation of myoblast. Moreover, circPTPN4 suppresses mitochondria biogenesis and activates fast-twitch muscle phenotype. Mechanistically, circPTPN4 can function as a ceRNA to regulate NAMPT expression by sponging miR-499-3p, thus participating in AMPK signaling.

Conclusions: circPTPN4 functions as a ceRNA to regulate NAMPT expression by sponging miR-499-3p, thus promoting the proliferation and differentiation of myoblast, as well as activating fast-twitch muscle phenotype.