Screening and analysis of differentially expressed circRNAs and miRNAs in chronic diabetic extremity wounds

Abstract

Increasing studies have shown that circular RNAs (circRNAs) and microRNAs (miRNAs) are related to the development of endocrine and metabolic diseases. However, there are few reports on the expression of circRNAs and miRNAs and their related co-expression and the expression of competitive endogenous RNA (ceRNA) in diabetic chronic refractory wounds. In this study, we compared the differential expression of circRNAs and miRNAs in diabetes chronic refractory wounds and normal skin tissues by high-throughput gene sequencing, and screened the differentially expressed circRNAs and miRNAs. Five abnormally expressed circRNAs and seven abnormally expressed miRNAs were detected by reverse transcription quantitative polymerase chain reaction PCR (RT-qPCR)to verify the results of RNA sequencing. We applied gene ontology (GO) to enrich and analyze dysregulated genes and elucidated their main functions via the Kyoto encyclopedia of genes and genomes analysis (KEGG). We constructed coding noncoding gene co-expression networks and ceRNA networks based on significantly abnormally expressed genes. According to the results of coding noncoding gene co-expression network analysis, hsa_circRNA_104175, hsa_circRNA_ 001588, hsa_circRNA_104330, hsa_circRNA_ 100141, hsa_circRNA_103107, and hsa_ circRNA_102044 may be involved in the regulation of the chronic intractable wound healing process in diabetes mellitus. This is particularly true in the regulation of vascular smooth muscle contraction-related pathways and the actin cytoskeleton, which affect the healing of chronic intractable wounds in diabetes. MiR-223-5p, miR-514a-3p, miR-205-5p, and miR-203-3p, which each have a targeting relationship with the above circRNAs, regulate the metabolism of nitrogen compounds in wound tissue by regulating NOD-like receptor signaling pathways, signaling pathways regulating the pluripotency of stem cells, microRNAs in cancer, and ECM-receptor interaction. This study showed circRNAs, miRNAs, and their network are associated with the development of chronic intractable wounds in diabetes, and our research identified the goals for new molecular biomarkers and gene therapy.