Expression profiles and bioinformatic analysis of microRNAs in myocardium of diabetic cardiomyopathy mice.

BACKGROUND

MicroRNAs (miRNAs) can regulate expression of target genes at post transcriptional level, and mediate the pathophysiological process of many diseases.

OBJECTIVE

The study will illuminate the miRNA expression profiles of diabetic cardiomyopathy (DCM), seeking probable biomarkers of DCM at early stage and determining a target for the treatment of DCM.

METHODS

Db/db mice were used as an animal model of type 2 diabetes mellitus. At 22 weeks of age, cardiac function was evaluated by echocardiography, and the structural changes in myocardium were evaluated by HE staining and TEM. The miRNA expression profiles were detected using miRNA sequencing and differentially expressed miRNAs were validated by real-time PCR. Bioinformatic analysis was used to analyze target genes of these miRNAs and relevant pathways in DCM.

RESULTS

The results showed that 40 miRNAs were differentially expressed, including 28 upregulated miRNAs and 12 downregulated miRNAs. GO and KEGG pathway analysis showed that the target genes of up-regulated miRNAs were involved in 66 pathways, including Wnt, p53 and calcium signaling pathways, as well as FOXO and apoptosis signaling pathways, etc. The target genes of down-regulated miRNAs were involved in 68 pathways, including mitophagy, Ras and MAPK signaling pathways, etc. Moreover, some differentially expressed miRNAs were found in myocardium of DCM for the first time, such as miR-7225-5p, miR-696, miR-3470a, miR-3470b, miR-6240, miR-6538, miR-5128, miR-1195, miR-203-3p and miR-330-5p.

CONCLUSIONS

It is hoped that a few novel molecular pathways or targets of treatment for DCM would be found through understanding the expression features of miRNAs in diabetic myocardium.