Combined analysis of circRNA and mRNA profiles and interactions in patients with Diabetic Foot and Diabetes Mellitus

Abstract

In order to elucidate the pathogenesis and explore new biomarkers for diabetes and diabetic foot (DF), an analysis using RNA sequencing affords broader insights into gene expression regulatory networks in DF. To better explore the molecular basis of DF, we carried out an analysis of circular RNA (circRNA) and messenger RNA (mRNA) expression profiles of serum samples from DF patients and diabetes mellitus (DM) patients. The potential roles and interactions of differentially expressed circRNAs and mRNAs were classified by gene ontology enrichment and Kyoto Encyclopedia of Genes and Genomes pathway analyses. Compared with diabetes patients, 279 mRNAs were upregulated and 353 mRNAs were downregulated in the serum of DF patients, and 33 circRNAs were differently expressed. The differential genes at the nodes of the interaction network were screened, and TLR6 RUNX1 and ST2 were found to be related to the progression of diabetes and DF. The enrichment pathway analysis revealed that the lysosomal pathway played a critical role in the occurrence and development of DF. TLR6, RUNX1, and ST2 mRNA expressions and the lysosomal pathway may be involved in the pathogenesis of diabetes and DF. In addition, methane metabolism and Chagas disease pathways were observed in the occurrence and development of DF, which is a new discovery in this study. This study provides clues on the molecular mechanisms of DF at the circRNA and mRNA levels.

Keywords: circRNA; diabetes mellitus; diabetic foot; mRNA.

FIGURE 1

Volcano plots of differentially expressed messenger RNAs (A) and circular RNAs (B)

FIGURE 2

Heatmap of differentially expressed circular RNAs

FIGURE 3

Heatmap of differentially expressed messenger RNAs

FIGURE 4

The interaction network of differentially expressed circular RNAs and target micro RNAs and messenger RNAs

FIGURE 5

Gene ontology enrichment analysis of downregulated (A) and upregulated (B) messenger RNAs and circular RNAs (C) of target genes

FIGURE 6

The bubble map of Kyoto Encyclopedia of Genes and Genomes enrichment analysis. A, Messenger RNAs (mRNAs) predicted by differentially expressed circular RNAs. B, differentially expressed mRNAs; the repeated pathways have been marked with red arrows)