25-hydroxycholesterol down-regulates oxysterol binding protein like 2 (OSBPL2) via the p53/SREBF2/NFYA signaling pathway
| Autor: | Changsong Lin, Quan Wang, Yajie Lu, Guangqian Xing, Hongshun Wang, Xin Cao, Qinjun Wei, Cui Zhang, Jun Yao |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Receptors Steroid Endocrinology Diabetes and Metabolism Clinical Biochemistry Down-Regulation Biochemistry 03 medical and health sciences 0302 clinical medicine Endocrinology RNA interference Transcription (biology) Humans Promoter Regions Genetic Molecular Biology Transcription factor Reporter gene Gene knockdown General transcription factor Chemistry Cell Biology Hydroxycholesterols Cell biology 030104 developmental biology CCAAT-Binding Factor 030220 oncology & carcinogenesis Molecular Medicine sense organs Tumor Suppressor Protein p53 Signal transduction Oxysterol-binding protein HeLa Cells Signal Transduction Sterol Regulatory Element Binding Protein 2 |
| Zdroj: | The Journal of Steroid Biochemistry and Molecular Biology. 187:17-26 |
| ISSN: | 0960-0760 |
| DOI: | 10.1016/j.jsbmb.2018.10.018 |
| Popis: | Oxysterol Binding Protein Like 2 (OSBPL2) is a lipid-binding protein implicated in various cellular processes. Previous studies have shown that depression of OSBPL2 significantly increases the level of cellular 25-hydroxycholesterol (25-OHC) which regulates the expression of lipid-metabolism-related genes. However, whether 25-OHC can regulate the expression of OSBPL2 remains unanswered. 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 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 signaling pathway. 25-OHC will accumulate over time in OSBPL2 knockdown cells. These results may provide a new insight into the deafness caused by OSBPL2 mutation. |
| Databáze: | OpenAIRE |
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