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

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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.", "claims": [{"id": "claim-data-access", "statement": "The data that support the findings of this study are available from the corresponding author upon reasonable request.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:33314661", "locator": "sections[26] \"DATA AVAILABILITY STATEMENT\" paragraph 2", "quote": "The data that support the findings of this study are available from the corresponding author upon reasonable request."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "partial", "objective": null, "steps": [{"id": "read_published_estimate", "order": 1, "name": "Read the published estimate from the source", "kind": "other", "state": "complete", "blocked_on": null, "description": "The claim, method and evidence span published with the source article.", "duration_hours": null, "parameters": {}, "inputs": ["source:pmid:33314661"], "outputs": ["the published estimate and its evidence"], "instruments": [], "reagents": []}, {"id": "obtain_source_data", "order": 2, "name": "Obtain the source data from the named repository", "kind": "data-preparation", "state": "blocked", "blocked_on": "data:accession_absent", "description": "The GEO series accession resolves and its sample accessions are listed. 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