MiR-199a-3p inhibits the proliferation, migration, and invasion of endothelial cells and retinal pericytes of diabetic retinopathy rats through regulating FGF7 via EGFR/PI3K/AKT pathway

Purpose:MiR-199a-3p is low expressed in diabetic retinopathy (DR). In the current study, we investigated the effects of miR-199a-3p on DR and the potential mechanisms. Methods:A DR rat model was established, and endothelial cells (ECs) and retinal pericytes (RPs) were extracted from the DR model rats to detect miR-199a-3p expression. Bioinformatics analysis predicted that fibroblast growth factor 7 (FGF7) was a target gene for miR-199a-3p, which was confirmed by dual-luciferase assay. Cell proliferation, migration, and invasion were detected by cell counting kit-8 (CCK-8), colony formation assay, wound-healing, and Transwell assay. Quantitative real-time polymerase chain reaction (q-PCR) and Western blot were performed to detect the expressions of mRNAs and proteins. Results:MiR-199a-3p was low expressed and FGF7 was high-expressed in ECs and RPs. Overexpressed miR-199a-3p suppressed the proliferation, migration, and invasion, and FGF7 expression of ECs and RPs. However, overexpression of FGF7 effectively eliminated the suppressive effects of miR-199a-3p overexpression malignant behaviors of the cells. Meanwhile, up-regulation of FGF7 noticeably reversed the phosphorylation of phosphoinositide 3-kinase (PI3K) and protein kinase B (AKT) and the expression of epidermal growth factor receptor (EGFR) reduced by miR-199a-3p. Conclusion:Our findings revealed that in the DR rat model, miR-199a-3p inhibited cell proliferation, migration, and invasion of EC and RP through targeting FGF7 and inhibiting the activation of the EGFR/PI3K/AKT pathway. This study may provide a new direction for the search for the treatment of DR.

Automated summary

MiR-199a-3p is downregulated in diabetic retinopathy (DR) and inhibits cell proliferation, migration, and invasion of endothelial cells (ECs) and retinal pericytes (RPs) by targeting fibroblast growth factor 7 (FGF7) and inhibiting the activation of the EGFR/PI3K/AKT pathway. This study may offer a new direction for the treatment of DR.