25-hydroxycholesterol down-regulates oxysterol binding protein like 2 (OSBPL2) via the p53/SREBF2/NFYA signaling pathway

This study aimed to explore the molecular mechanism of 25-OHC regulating the expression of OSBPL2. Using dual-luciferase reporter assay, we found a decrease of nuclear transcription factor Y subunit alpha (NFYA) bound with OSBPL2 promoter when HeLa cells were treated with by 25-OHC. Furthermore, transcriptome sequencing and RNA interference results revealed that the p53/sterol regulatory element binding transcription factor 2 (SREBF2) signaling pathway was involved in the NFYA-dependent transcription of OSBPL2 induced by 25-OHC. Based on these results, we concluded that pleomorphic adenoma gene 1 (PLAG1) and NFYA participated in the basal transcription of OSBPL2 and that 25-OHC decreased the transcription of OSBPL2 via the p53/SREBF2/NFYA pathway. 25-OHC will accumulate over time in OSBPL2 knockdown cells. These results may a new insight into the deafness caused by OSBPL2 mutation.Graphical abstracts
Source: The Journal of Steroid Biochemistry and Molecular Biology - Category: Biochemistry Source Type: research