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Circular RNAs related to skeletal muscle atrophy in diabetic mouse model(PDF)

Journal of Shenzhen University Science and Engineering[ISSN:1000-2618/CN:44-1401/N]

2022 Vol.39 No.3(237-362)
Research Field:


Circular RNAs related to skeletal muscle atrophy in diabetic mouse model
YANG Lei1 WANG Yun1 DENG Fang1 XU Te1 GOU Deming1 ZHOU Wei1 HU Zhangli1 and ZOU Xianghui2
1) College of Life Sciences and Oceanography, Shenzhen University, Shenzhen 518071, Guangdong Province, P. R. China
2) College of Food Engineering and Biotechnology, Hanshan Normal University, Chaozhou 521041, Guangdong Province, P. R. China
bioinformatics diabetes molecular pathology muscle atrophy biomarkers circular ribonucleic acids (circRNAs)
Skeletal muscle atrophy is one of the serious complications of diabetes mellitus, but its molecular pathogenesis remains unclear. In this study, the type 1 diabetes mellitus of mouse model was induced by intraperitoneal injection with streptozotocin, and high-throughput sequencing was used to investigate the expression profile of circular ribonucleic acids (circRNAs) associated with diabetic muscular atrophy in this model. The roles of circRNA during diabetic skeletal muscle atrophy were explored by using bioinformatics analysis. The profiles of circRNA in gastrocnemius muscle of streptozotocin-induced diabetic mice were detected. Results showed that, compared with the same tissue of normal isogenic background mice, the gastrocnemius muscle of diabetic mice showed: (a) the areas of muscle fiber were significantly reduced, and the grasping power and motor function were decreased; (b) there were 1 403 differentially expressed circRNAs in skeletal muscles of diabetes model, of which 690 were up-regulated and 713 were down-regulated; and (c) these disease related candidate circRNAs matched parent genes were revealed by the functional enrichment analyses of gene ontology (GO) and kyoto encyclopedia of genes and genomes (KEGG). The most enriched GO terms were "transcriptional regulation", "cytoplasmic components" and "protein binding". The KEGG enriched signaling pathways were "mitogen-activated protein kinase", "ubiquitin-mediated proteolysis", "forkhead box protein O" and others related to muscular atrophy of diabetics. Using databases and bioinformatic analysis, downstream effectors-micro RNAs binding to MuRF1 (a reported muscular dystrophy gene) and their upstream regulators-circRNAs were discovered. Thus, the potential molecular response axis and interaction network of circRNA-miRNA-mRNA for muscular atrophy of diabetes were constructed. The results suggest that circRNAs related to muscle atrophy have potential to regulate key molecules in pathogenesis of diabetes.


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