Analysis of circRNA expression profile and functional enrichment of myocardial mitochondria in mice with diabetic cardiomyopathy / 西安交通大学学报(医学版)

ABSTRACT

【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, chrM1207-1536+, was associated with miR-491-3p, miR-99a-3p, and miR-99b-3p, and the most significantly down-regulated circRNA, chrM1453-3205+, 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.