Abstract
Duchenne muscular dystrophy (DMD) is an X-linked genetic neuromuscular disease that is characterized by progressive muscle wasting and by defects in the regenerative capacity and inflammatory infiltration of muscle. Many noncoding RNAs (ncRNAs) participate in the pathophysiological mechanisms of this disease. To explore the role of circular RNAs (circRNAs), a type of ncRNAs, in DMD, microarray analysis was performed to explore the expression patterns of circRNAs in the gastrocnemius muscles in mdx mice, a DMD animal model, and C57 mice. The microarray data were validated by qRT-PCR. Further, gene ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were performed to predict the function of the differentially expressed circRNAs (DEcRNAs). A circRNA/microRNA (miRNA) interaction network was predicted by bioinformatics. We also predicted the protein-coding ability of the circRNAs based on their N6-methyladenosine motifs and open-reading frames. We identified 197 differentially expressed circRNAs between mdx mice and C57 mice. Of the 197 DEcRNAs, 6 circRNAs were randomly selected to validate the microarray data, and twenty-two circRNAs were randomly selected to construct a circRNA/miRNA interaction network. Bioinformatics analysis showed that the linear counterparts of the DEcRNAs were mainly associated with muscle structure, nervous system development, and the cAMP signaling pathway. A total of 189 circRNAs were predicted to have protein-coding potential, and there were 98 circRNAs that could potentially be translated into polypeptides with 150 or more amino acids. This work described the expression pattern of circRNAs in mdx mice and indicated that circRNAs may play pivotal roles in the pathophysiological mechanisms of DMD.
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Acknowledgments
The authors would like to thank Jinfu Lin, Hongjie Li, Jingyan Chen, and Baihong Dong for their technical assistance.
Funding
The work was supported by the grants from the Natural Science Foundation of Guangdong Province (2017A030313850); the Natural Science Foundation of Guangdong Province (2016A030310283); the National Natural Science Foundation of China (81701240); Guangdong Provincial Key Laboratory for Diagnosis and Treatment of Major Neurological Diseases (2017B030314103); The Southern China International Cooperation Base for Early Intervention and Functional Rehabilitation of Neurological Diseases (2015B050501003); Guangdong Provincial Engineering Center for Major Neurological Disease Treatment; and Guangdong Provincial Translational Medicine Innovation Platform for Diagnosis and Treatment of Major Neurological Disease.
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Song, Z., Liu, Y., Fang, X. et al. Comprehensive analysis of the expression profile of circRNAs and their predicted protein-coding ability in the muscle of mdx mice. Funct Integr Genomics 20, 397–407 (2020). https://doi.org/10.1007/s10142-019-00724-w
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DOI: https://doi.org/10.1007/s10142-019-00724-w