杨雷,王筠,邓芳,等.糖尿病鼠骨骼肌萎缩相关环状RNA的研究[J].深圳大学学报理工版,2022,39(3):262-270.[doi:10.3724/SP.J.1249.2022.03262]
YANG Lei,WANG Yun,DENG Fang,et al.Circular RNAs related to skeletal muscle atrophy in diabetic mouse model[J].Journal of Shenzhen University Science and Engineering,2022,39(3):262-270.[doi:10.3724/SP.J.1249.2022.03262]
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糖尿病鼠骨骼肌萎缩相关环状RNA的研究
杨雷1，王筠1，邓芳1，许特1，苟德明1，周威1，胡章立1，邹湘辉2

1.深圳大学生命与海洋科学学院，广东深圳518071;2.韩山师范学院生命科学与食品工程学院，广东潮州521041

生物信息学;糖尿病;分子病理;肌萎缩;生物标志物;环状核糖核酸

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)

DOI: 10.3724/SP.J.1249.2022.03262

备注

骨骼肌萎缩是糖尿病患者中、晚期严重并发症之一，为研究其分子发病机制，利用链脲佐菌素诱导构建小鼠1型糖尿病模型，通过高通量测序技术，调查与糖尿病肌萎缩病变相关的环状核糖核酸（circularribonucleicacid，circRNA）表达谱，并利用生物信息分析软件探究circRNA在糖尿病骨骼肌萎缩病变中的可能作用．结果显示，与正常同基因背景小鼠的同类组织相比，糖尿病鼠的腓肠肌呈现：①肌纤维面积明显减小，运动功能下降；②含有1403个与1型糖尿病发生发展相关的差异表达circRNA，其中，690个上调和713个下调；③通过基因本体、京都基因和基因组百科全书的功能富集分析显示，差异表达的候选circRNA亲本基因主要富集于转录调节生物学过程、细胞质成分和蛋白质结合分子功能等方面，以及促分裂原活化蛋白激酶信号通路、泛素介导的蛋白降解、叉头盒蛋白O通路与糖尿病肌萎缩相关的信号通路等．通过数据库信息和生物信息分析技术，预测与肌萎缩基因MuRF1相结合的小RNA（mircoRNA，miRNA），并挖掘出可调控它们表达的功能circRNA，构建了circRNA-miRNA-mRNA的潜在分子调控反应轴和互作网络．研究结果表明，与肌萎缩相关的circRNA在糖尿病发病中具有调控关键分子的潜能．
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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