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

Abstract

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.

Diabetic Wound-Healing Science

“…A number of serum biomarkers have been identified, including albumin [ 257 ], PLR and NLR [ 122 , 258 ], angiopoietin-like 2 (ANGPTL2) [ 259 ], lipoprotein-associated phospholipase A2 and interleukin-18 (IL-18) [ 260 ], pentraxin 3 [ 261 ], T-cell differentiation markers [ 262 ], stem/progenitor cells [ 263 ], as well as neutrophil extracellular traps (NETs)-specific markers [ 264 ]. Recent genomic analyses of DFU have utilized circRNAs [ 265 , 266 , 267 ], lncRNAs [ 268 ], miRNAs [ 99 , 100 , 269 ], genetic polymorphisms [ 270 , 271 , 272 ], cytokine arrays [ 273 ], and network maps [ 274 ] for the identification of other potential biomarkers for DFU diagnosis and prognosis. With the advent of bioinformatic analyses predicting factors for diabetic complications [ 275 ], the integration of computational algorithms with clinical observations and biomarker results will likely become the new standard for DFU care.…”

Circular RNA: A promising new star for the diagnosis and treatment of colorectal cancer

“…That is, through the interaction of circRNAs-miRNAs and miRNAs-mRNAs, a circRNAs-miRNAs-mRNAs regulatory network is formed to participate in the occurrence and development of CRC. [81][82][83][84] Hsa-circ-0000284 is derived from exon 2 of linear HIPK3, called circHIPK3, which is highly expressed in CRC and mainly expressed in the cytoplasm. Therefore, we conclude that circHIPK3 may play a positive regulatory role in the tumorigenesis of CRC by sponging miR-1207-5p, which directly targets FMNL2.…”

Heterogeneous miRNA-mRNA Regulatory Networks of Visceral and Subcutaneous Adipose Tissue in the Relationship Between Obesity and Renal Clear Cell Carcinoma

“…In accordance with the annotations, probe IDs in the matrix file were transformed into the gene symbols, and probes that did not correspond to the mRNA symbols were excluded. The average value of mRNA correlated with more than one probe was used as the final expression value ( 28 ). We then normalized the data of mRNA expression profiles using robust multi-array average (RMA) based on the limma package in R (v.4.0.3) software ( 29 ).…”