Basing on microRNA-mRNA analysis identifies microRNA in exosomes associated with wound repair of diabetic ulcers

Abstract

The diabetic ulcer is one of the serious complications of diabetes. In this study, we aimed to establish an exosomal microRNA (miRNA)-targeted messenger RNA (mRNA) regulatory network for screening new biomarkers for diabetic ulcer treatment. For this purpose, exosomes were extracted from bone marrow stem cells (BMSCs) collected from diabetic ulcer patients and healthy adults. The miRNAs in exosomes was detected by high-throughput sequencing analysis. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis of the differential miRNAs were performed. The miRNA-mRNA regulatory network between candidate miRNAs and their target genes were constructed by Cytoscape software basing on mRNA expression profiles data of diabetic ulcer patients from Gene Expression Omnibus (GEO). GO and KEGG analyses of the core genes were performed. A total of 63 differential expressed miRNAs in BMSCs exosomes were identified between diabetic ulcer patients and healthy adults. The GO analysis of miRNAs showed that it was mainly related to signal transduction and intercellular transport, and KEGG analysis showed that it was related to the vascular endothelial growth factor (VEGF) signaling pathway. The core genes of the miRNA-mRNA network were thioredoxin interacting protein (TXNIP), cell division cycle 14A (CDC14A), cache domain containing 1 (CACHD1), interferon-induced protein 44 like (IFI44L), late cornified envelope 1AL (CE1A), leucine-rich repeats and immunoglobulin-like domains 2 (LRIG2), palmdelphin (PALMD) and serine and arginine-rich splicing factor 11 (SRSF11). GO analysis of the core genes was related to platelet-derived growth factor receptor signaling pathway. The KEGG analysis of the core genes was related to the cell cycle and nucleotide-binding oligomerization domain (NOD)-like receptor signaling pathway. A potential miRNA-mRNA regulatory network provides a comprehensive understanding of the molecular mechanisms and promising new targets such as miR-130a-5p, SESN2, LRIG2, and CDC14A for the wound repair of diabetic ulcers.