糖尿病性心肌病小鼠心肌线粒体circRNA表达谱与功能富集分析  

Analysis of circRNA expression profile and functional enrichment of myocardial mitochondria in mice with diabetic cardiomyopathy

作　　者：王毅[1] 尤红俊 韩稳琦 刁佳宇 WANG Yi;YOU Hongjun;HAN Wenqi;DIAO Jiayu(The Second Cardiovascular Medicine Department of Shaanxi Provincial People’s Hospital,Xi’an 710051,China)

机构地区：[1]陕西省人民医院心内二科,陕西西安710051

出　　处：《西安交通大学学报（医学版）》2023年第5期701-708,共8页Journal of Xi’an Jiaotong University（Medical Sciences）

基　　金：陕西省人民医院科技人才支持计划项目(2021BJ-27)。

摘　　要：目的探索糖尿病性心肌病(diabetic cardiomyopathy,DCM)小鼠心肌线粒体circRNA的差异表达情况及其功能分析。方法以16周龄的db/db小鼠构建DCM小鼠模型,C57BL/KsJ小鼠作为对照。提取两组小鼠心肌组织RNA,高通量测序筛选两组差异表达的线粒体circRNA,使用RT-qPCR对差异表达显著的前10个circRNA验证测序结果,并对差异表达circRNA靶基因作功能富集分析,使用miRNA靶标预测软件对circRNA-miRNA共表达网络分析。结果与对照组比较,DCM组小鼠心肌中147个差异表达的线粒体circRNA,其中高表达89个、低表达58个。差异表达circRNA在组织中的表达变化与测序结果趋势一致。GO与KEGG富集分析显示,差异表达的circRNA靶基因主要富集在cGMP/PKG、胰高血糖素等通路,与线粒体能量代谢、心肌肥大相关。circRNA-miRNA共表达网络分析发现,表达上调最显著的chrM:1207-1536+与miR-491-3p、miR-99a-3p、miR-99b-3p有关联,表达下调最显著的chrM:1453-3205+与miR-181b-1-3p、miR-181b-2-3p、miR-672-5p有关联。结论DCM小鼠心肌线粒体存在差异表达的circRNA,且可能与相应miRNA相互作用,通过调节能量代谢、凋亡等通路影响心肌纤维化、心肌细胞肥大,从而参与DCM的发病。Objective To explore the differential expression and functional analysis of circRNA from myocardial mitochondria in diabetes cardiomyopathy(DCM)mice.Methods The DCM mice model was established in 16-week-old db/db mice,and C57BL/KsJ mice were used as controls.RNA was extracted from the myocardium of two groups of mice,high-throughput sequencing was used to screen mitochondrial circRNA differentially expressed in the two groups,RT-qPCR was used to verify the sequencing results of the first 10 circRNAs with significant differential expression,and functional enrichment analysis was performed on the differentially expressed circRNA target genes,and miRNA target prediction software was used to analyze the circRNA-miRNA co-expression network.Results There were 147 mitochondrial circRNAs differentially expressed in the myocardium of DCM mice,including 89 highly expressed and 58 low expressed.The expression pattern of differentially expressed circRNAs in tissues was consistent with those of sequencing results.The enrichment analysis of GO and KEGG showed that the differentially expressed circRNA target genes were mainly enriched in cGMP/PKG,glucagon pathways,which were related to mitochondrial energy metabolism and cardiac hypertrophy.circRNA-miRNA co-expression analysis found that the most significantly up-regulated circRNA,chrM:1207-1536+,was associated with miR-491-3p,miR-99a-3p,and miR-99b-3p,and the most significantly down-regulated circRNA,chrM:1453-3205+,was associated with miR-181b-1-3p,miR-181b-2-3p,and miR-672-5p.Conclusion Compared to the control mice,there is differential expression of circRNAs in myocardial mitochondria of DCM mice.The differentially expressed circRNAs may interact with the corresponding miRNA to affect myocardial fibrosis and hypertrophy through regulation of energy metabolism,apoptosis and other pathways,thus participating in the pathogenesis of DCM.

关 键 词：糖尿病性心肌病 线粒体 circRNA 

分 类 号：R34[医药卫生—基础医学]