linc00174-EZH2-ZNF24/Runx1-VEGFA Regulatory Mechanism Modulates Post-burn Wound Healing
| Autor: | Pengfei Liang, Licheng Ren, Jizhang Zeng, Xu Cui, Xiao-yuan Huang, Xu Huang, Le Guo, Mitao Huang, Bimei Jiang, Situo Zhou, Minghua Zhang, Pihong Zhang |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
VEGFA Angiogenesis wound healing macromolecular substances Article 03 medical and health sciences Histone H3 angiogenesis 0302 clinical medicine Downregulation and upregulation Runx1 Drug Discovery EZH2 Tube formation Chemistry lcsh:RM1-950 ZNF24 Cell biology Vascular endothelial growth factor A 030104 developmental biology lcsh:Therapeutics. Pharmacology 030220 oncology & carcinogenesis heat denature linc00174 Molecular Medicine Wound healing Chromatin immunoprecipitation |
| Zdroj: | Molecular Therapy: Nucleic Acids, Vol 21, Iss, Pp 824-836 (2020) Molecular Therapy. Nucleic Acids |
| ISSN: | 2162-2531 |
| Popis: | 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, RNA chromatin immunoprecipitation (ChIP) sequencing analysis revealed upregulation of long intergenic non-coding RNA 00174 (linc00174) in the post-burn tissues. linc00174 overexpression promoted angiogenic activities of human umbilical vein endothelial cells (HUVECs) in the heat-denatured cell model, characterized by the promotion of cell proliferation, migration, and tube formation. Mechanistically, linc00174 directly bound to enhancer of zeste homolog 2 (EZH2), thus stimulating the protein level of trimethylation at lysine 27 of histone H3 (H3K27me3). Moreover, inhibition of EZH2 resulted in downregulation of ZNF24 and Runx1, as well as a decline of vascular endothelial growth factor A (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 the facilitation of angiogenesis during the recovery of heat-denatured endothelial cells. Graphical Abstract In the present study, we discovered that upregulation of linc00174 promotes endothelial cell-mediated angiogenesis by a mechanism of the linc00174-EZH2-ZNF24/Runx1-VEGFA regulatory axis, and it facilitates post-burn wound healing. This discovery provides a new regulation of post-burn wound healing, and we elicited a new role of linc00174 in the regulation of angiogenesis. |
| Databáze: | OpenAIRE |
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