HIF‐1α‐induced expression of the m6A reader YTHDF1 inhibits the ferroptosis of nucleus pulposus cells by promoting SLC7A11 translation

• DOI: 10.1111/acel.14210
• Publication Date: 2024-05-24T06:30:23Z
• Authors: Xiao Lu; Dachuan Li; Zhidi Lin; Tian Gao; Zhaoyang Gong; Yuxuan Zhang; Hongli Wang; Xinlei Xia; Feizhou Lu; Jian Song; Guangyu Xu; Jianyuan Jiang; Xiaosheng Ma; Fei Zou
• Keywords: Chromatin immunoprecipitation

The nucleus pulposus is in a hypoxic environment the human body, and when intervertebral disc degeneration (IVDD) occurs, disrupted. Nucleus cell (NPC) ferroptosis one of causes IVDD. N6-methyladenosine (m6A) its reader protein YTHDF1 regulate cellular activities by affecting RNA metabolism. However, regulation NPCs m6A-modified RNAs under conditions has not been as well studied. In this study, through vitro vivo experiments, we explored underlying mechanism HIF-1α regulating NPCs. results indicated that overexpression or suppressed NPC ferroptosis; conversely, knockdown increased levels Luciferase reporter assays chromatin immunoprecipitation demonstrated regulated transcription directly binding to promoter region. Polysome profiling showed promoted translation SLC7A11 consequently expression anti-ferroptosis GPX4 mRNA. conclusion, HIF-1α-induced reduces delays IVDD promoting m6A-dependent manner.