Identification of potential circRNAs and circRNA‐miRNA‐mRNA regulatory network in the development of diabetic foot ulcers by integrated bioinformatics analysis

We aimed to explore the mechanism of circular RNAs (circRNAs) and provide potential biomarkers for molecular therapy of diabetic foot ulcers (DFU). Gene expression profile of GSE114248, including five normal samples and five DFU samples, was downloaded from GEO database. Differentially expressed circRNAs (DEcircRNAs) between two groups were identified. Then, DEcircRNA‐miRNA and miRNA‐mRNA interaction was revealed, followed by the circRNA‐miRNA‐mRNA network construction. Moreover, functional and pathway analysis were performed based on mRNAs, followed by the DM‐related pathway exploration. Specific binding sites for key circRNAs and associated miRNAs were under investigation. Finally, RT‐qPCR was used to verify the candidate the relative expression level of circRNA between normal tissues and DFU. Totally, 65 DEcircRNAs were revealed between two groups, followed by 113 circRNA‐miRNA‐mRNA interactions explored. The mRNAs in these interactions were mainly assembled in functions like cell proliferation and pathways. Moreover, a total of 11 DM‐related pathways were revealed. Finally, circRNA‐miRNA specific binding‐site analysis revealed two key circRNAs, for example, circRNA_072697 and circRNA_405463, corresponding to their miRNAs. These two circRNAs were novel biomarkers for DFU. circRNA_072697 acted as a sponge of miR‐3150a‐3p in the progression of DFU via regulating KRAS. MAPK signaling pathway might contribute to the development of DFU.