linc00174-EZH2-ZNF24/Runx1-VEGFA regulatory mechanism modulates post-burn wound healing

Abstract Preservation of denatured dermis exerts promotive functions in wound healing and improves the appearance and function of skin. Angiogenesis is crucial for wound healing during burn injury. However, the potential molecular mechanism of angiogenesis in the recovery after burn injury remains to be elucidated. Herein, the RNA Chip-sequencing analysis revealed up-regulation of linc00174 in the post-burn tissues. linc00174 overexpression promoted angiogenic activities of HUVECs in the heat-denatured cell model, characterized by the promotion of cell proliferation, migration and tube formation. Mechanistically, linc00174 directly bound to EZH2, thus stimulating the protein level of H3K27me3. Moreover, inhibition of EZH2 resulted in down-regulation of ZNF24 and Runx1, as well as a decline of VEGFA. Furthermore, EZH2 modulated epigenetic repression of ZNF24 and Runx1 through the promoter of H3K27me3. Additionally, ZNF24 and Runx1 both functioned as transcriptional inhibitors of VEGFA. Taken together, these findings uncover that linc00174 epigenetically inhibits ZNF24 and Runx1 expression through binding to EZH2, thus attenuating the suppression of VEGFA, contributing to facilitate angiogenesis during the recovery of heat-denatured endothelial cells.