Bioinformatics Analysis for Identifying Micro-RNAs, Long Noncoding RNAs, Transcription Factors, Immune Genes Regulatory Networks, and Potential Therapeutic Agents for Diabetic Cardiomyopathy Using an Integrated Bioinformatics Analysis

Objectives

We identified functional genes and studied the underlying molecular mechanisms of diabetic cardiomyopathy (DCM) using bioinformatics tools.

Methods

Original gene expression profiles were obtained from the GSE21610 and GSE112556 datasets. We used GEO2R to screen the differentially expressed genes (DEGs). Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were performed on DEGs. Protein–protein interaction (PPI) networks of DEGs were constructed using STRING and hub genes of signaling pathways were identified using Cytoscape. Aberrant hub gene expression was verified using The Cancer Genome Atlas dataset. Connectivity Map was used to predict the drugs that could treat DCM.

Results

The DEGs in DCM were mainly enriched in the nuclei and cytoplasm and involved in DCM- and chemokine-related signaling pathways. In the PPI network, 32 nodes were chosen as hub nodes and an RNA interaction network was constructed with 517 interactions. The expression of key genes (JPIK3R1, CCR9, XIST, WDFY3.AS2, hsa-miR-144-5p, and hsa-miR-146b-5p) was significantly different between DCM and normal tissues. Danazol, ikarugamycin, and semustine were identified as therapeutic agents against DCM using CMAP.

Conclusion

The identified hub genes could be associated with DCM pathogenesis and the above drugs could be used for treating DCM.