Identification of a potentially functional circRNA-miRNA-mRNA regulatory network in type 2 diabetes mellitus by integrated microarray analysis.

BACKGROUND

Circular RNAs (circRNAs) function as miRNA sponges by adsorbing microRNAs (miRNAs), thereby regulating messenger RNA (mRNA) expression. The circRNA-miRNA-mRNA regulatory network associated with type 2 diabetes mellitus (T2DM) has rarely been explored. A circRNA-miRNA-mRNA regulatory network associated with T2DM was established to help deepen our understanding of the molecular mechanism of and therapeutic targets for T2DM.

METHODS

Differentially expressed circRNAs (DEcircRNAs), miRNAs (DEmiRNAs), and mRNAs (DEmRNAs) were derived from the Gene Expression Omnibus (GEO) microarray datasets GSE114248, GSE51674 and GSE95849, respectively. A circRNA-miRNA-mRNA regulatory network associated with T2DM and its subnetwork were constructed. The hub genes were screened using a protein-protein interaction (PPI) network. Finally, a hub gene-related network was constructed. Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed.

RESULTS

The circRNA-miRNA-mRNA network included 9 circRNAs, 24 miRNAs and 320 mRNAs. When four key circRNAs (circMYO9B, circGRAMD1B, circTHAP4 and circTMC7) were chosen, the subnetwork contained 4 circRNAs, 18 miRNAs and 307 mRNAs. Afterwards, 8 hub genes (SIRT1, GNG7, KDR, FOS, SIN3B, STAT1, SP1, and MAPK3) were extracted from the PPI network. GO and KEGG pathway analyses revealed that the network might be involved in oxidative stress responses, regulation of inflammation, neovascularization, endocrine and cancer-related processes, etc.

CONCLUSIONS

A circRNA-miRNA-hub gene regulatory network was constructed, and the potential functions of the hub genes were analyzed. Four important circRNAs (circMYO9B, circGRAMD1B, circTHAP4 and circTMC7) might be involved in the occurrence and development of T2DM, and this finding provides new insight into the molecular mechanism of and therapeutic targets for T2DM and its complications. Future studies are needed to validate the sponge effects and mechanisms of these 4 circRNAs.