EP300 attenuates ferroptosis and stimulates proliferation, migration, and fibrosis of keloid fibroblasts via YY1/GPX4 axis.

Abstract

The aim of this investigation was to identify the hub genes associated with ferroptosis in keloid. We analyzed the correlation between differentially expressed genes Yin Yang-1 (YY1) and glutathione peroxidase-4 (GPX4) with keloid by quantitative Real‑Time PCR and Western blot. Molecular biological experiments were conducted to identify the role of YY1 and GPX4 in human keloid fibroblasts (HKFs). glutathione and oxidized glutathione kit, Malondialdehyde Assay Kit and C11-BODIPY (581/591) fluorescence probe were applied to monitor ferroptosis. Gain-of-function and loss-of-function assay demonstrated that YY1 regulated proliferation, migration, fibrosis of HKFs in vitro. YY1 bind to the promoter sequence of target gene GPX4. YY1-induced HKFs ferroptosis was dependent on GPX4 pathway. Furthermore, we discovered that the UCSC Genome Browser Database included an enrichment of H3K27ac signals at the YY1 promoter region. The inhibition of proliferation, migration, fibrosis, and the activation of ferroptosis in knockdown of YY1 HKFs was reversed by EP300 overexpression.