Mechanism of EZH2-mediated histone methylation promoting bFGF-induced angiogenesis of human umbilical vein endothelial cells.

This study aims to explore the role of enhancer of zeste homolog 2 (EZH2)-mediated histone methylation in basic fibroblast growth factor (bFGF)-induced angiogenesis of human umbilical vein endothelial cells (HUVECs). EZH2, vascular endothelial growth factor A (VEGFA), miR-340-5p, and nuclear factor-erythroid 2-related factor 2 (NRF2) expressions in bFGF-induced HUVECs were detected by real-time quantitative polymerase chain reaction (RT-qPCR) and Western blot. After transfection of EZH2 siRNA, NRF2 siRNA, or miR-340-5p inhibitor, cell migration and angiopoiesis were assessed by Transwell and tube formation assays. Chromatin immunoprecipitation (ChIP) was performed to analyze the enrichment of EZH2 or trimethylated H3 lysine 27 (H3K27me3) on NRF2 promoter. The binding between NRF2 and miR-340-5p was verified by ChIP and dual-luciferase assay. EZH2 was highly expressed while miR-340-5p and NRF2 were poorly expressed in bFGF-induced HUVECs. Silence of EZH2 restrained HUVEC migration, and reduced the number of branches and tube length. Mechanically, EZH2 enhances the enrichment of H3K27me3 on the NRF2 promoter, thereby repressing NRF2 expression and further leading to transcriptional repression of miR-340-5p. In conclusion, EZH2 inhibits the NRF2/miR-340-5p axis and promotes bFGF-induced angiogenesis of HUVECs by increasing the H3K27me3 modification on the NRF2 promoter.