Vitamin D regulates the gene expression through competing endogenous RNAs networks in high glucose-treated endothelial progenitor cells

Objective: Vitamin D (vit-D) supplementation can improve endothelial cell function in type 2 diabetes mellitus (DM) patients with vit-D insufficiency or deficiency. In the present study, we aimed to compare the expression profiles of circRNAs, lncRNAs, miRNAs, and mRNAs between vit-D-treated endothelial progenitor cells (EPCs) and control cells, and to further construct the vit-D-regulated ceRNA networks in EPCs.Methods: RNA sequencing was performed on the vit-D-treated EPCs and control cells derived from the bone marrow (BM). Bioinformatics analyses were performed to identify differentially expressed (DE) miRNAs, circRNAs, mRNAs, and lncRNAs. Then Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were conducted to predict the function of genes. Competing endogenous RNA (ceRNA) networks were constructed with Cytoscape software.Results: Vit-D application induced changes in the expression profiles of 1791 mRNAs, 2726 lncRNAs, 205 circRNAs, and 45 miRNAs in EPCs treated with high levels of glucose. These DE RNAs were associated with MMP and GTPase activities, specific signaling pathways, and components of actin, extracellular matrix, or adherens junction. DE circRNAs, which functioned independently of their linear host genes, interacted with miRNAs to serve as miRNA sponges in complex ceRNA networks.Conclusions: The data indicates that circRNAs and lncRNAs comprise ceRNAs to sponge effects of miRNAs on the expressions of mRNAs following vit-D application in EPCs. Vit-D improves the function of EPCs via associated ceRNA interaction networks in diabetes patients.