Details

Autor(en) / Beteiligte

• Xiao, Feng-Jun
• Zhang, Dan
• Wu, Ye
• Jia, Qing-Hua
• Zhang, Lin
• Li, Yu-Xiang
• Yang, Yue-Feng
• Wang, Hua
• Wu, Chu-Tse
• Wang, Li-Sheng

Titel

miRNA-17-92 protects endothelial cells from erastin-induced ferroptosis through targeting the A20-ACSL4 axis

Ist Teil von

• Biochemical and biophysical research communications, 2019-07, Vol.515 (3), p.448-454

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2019

Link zum Volltext

Quelle

Alma/SFX Local Collection

Beschreibungen/Notizen

• Endothelial cell death is linked to vascular diseases such as atherosclerosis and tissue ischemia. miRNA-17-92 (miR-17–92) is a multiple functional oncogenic miRNA cluster which plays vital roles in tumor angiogenesis and tissue development. However, its role in regulation of endothelial cell ferroptosis remains unclear. In this study, we revealed that miR-17–92 protects endothelial HUVEC cells from erastin-induced ferroptosis. miR-17-92 overexpression significantly reduced erastin-induced growth inhibition and ROS generation of HUVEC cells. Furthermore, Zinc lipoprotein A20, a validated target of miR-17-92, was identified as a novel regulator of endothelial cell ferroptosis. Lentivirus mediated A20 overexpression increased ROS generation and enhanced erastin-induced ferroptosis, whereas A20 knockdown inhibited erastin-induced ferroptosis. Mechanistic studies revealed that erastin-induced ferroptosis is associated with GPX4 downregulation and ACSL4 upregulation. miR-17-92 overexpression or A20 inhibition increased the ACSL4 expression in HUVEC cells. A20 was identified to directly with and regulate ACSL4 expression by immunoprecipitation. It suggests that the A20-ACSL4 axis plays important roles in erastin-induced endothelial ferroptosis. In conclusion, this study revealed a novel mechanism through which miR-17-92 protects endothelial cells from erastin-induced ferroptosis by targeting the A20-ACSL4 axis. •miR-17-92 protects endothelial cells from erastin-induced ferroptosis.•Zinc lipoprotein A20 is identified as a novel regulator of ferroptosis.•A20 regulates ACSL4 by their directly interaction in endothelial cells.•miR-17-92 targets the A20-ACSL4 axis in endothelial cells.