LincRNA Plays a Role in the Effect of CYP46A1 Polymorphism in Alzheimer’s Disease – Related Pathology
Polymorphism of the cholesterol-24S-hydroxylase (CYP46A1) gene is thought to be a risk factor for Alzheimer’s disease (AD). A single nucleotide polymorphism (T/C) in intron 2, rs754203, has been confirmed to be implicated in AD. Rs754203 is located in the long intronic non-coding RNA (LincRNA) seque...
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doaj-83a6341d5544437a9ad3986c0cbab2a92020-11-25T02:47:36ZengFrontiers Media S.A.Frontiers in Aging Neuroscience1663-43652020-01-011110.3389/fnagi.2019.00381486760LincRNA Plays a Role in the Effect of CYP46A1 Polymorphism in Alzheimer’s Disease – Related PathologyYang Chen0Hui-Yun Li1Fan Zeng2Le Chen3Fa-Ying Zhou4Ze-Yan Peng5Hai Yang6Hua-Dong Zhou7Yan-Jiang Wang8Ling Li9Department of Neurology, Centre for Clinical Neuroscience, Daping Hospital of Army Medical University, Chongqing, ChinaDepartment of Neurology, Centre for Clinical Neuroscience, Daping Hospital of Army Medical University, Chongqing, ChinaDepartment of Neurology, Centre for Clinical Neuroscience, Daping Hospital of Army Medical University, Chongqing, ChinaPostgraduate School, Bengbu Medical College, Bengbu, ChinaDepartment of Neurology, Centre for Clinical Neuroscience, Daping Hospital of Army Medical University, Chongqing, ChinaDepartment of Neurology, Centre for Clinical Neuroscience, Daping Hospital of Army Medical University, Chongqing, ChinaDepartment of Neurology, Centre for Clinical Neuroscience, Daping Hospital of Army Medical University, Chongqing, ChinaDepartment of Neurology, Centre for Clinical Neuroscience, Daping Hospital of Army Medical University, Chongqing, ChinaDepartment of Neurology, Centre for Clinical Neuroscience, Daping Hospital of Army Medical University, Chongqing, ChinaDepartment of Neurology, Centre for Clinical Neuroscience, Daping Hospital of Army Medical University, Chongqing, ChinaPolymorphism of the cholesterol-24S-hydroxylase (CYP46A1) gene is thought to be a risk factor for Alzheimer’s disease (AD). A single nucleotide polymorphism (T/C) in intron 2, rs754203, has been confirmed to be implicated in AD. Rs754203 is located in the long intronic non-coding RNA (LincRNA) sequence, which has previously been shown to be involved in the pathology of many diseases. Thus, the present study aimed to investigate the role of LincRNA in the CYP46A1 gene expression and related AD pathology. SH-SY5Y cells with overexpressed TT or CC genotype CYP46A1 were used. Through RT-PCR, Western blot and ELISA assays, we found that LincRNA can affect the CYP46A1 gene expression and the production of 24-OHC and Aβ. Overexpression of LincRNA can significantly inhibit CYP46A1 expression and 24-OHC production, as well as increasing the Aβ expression level. Silencing of LincRNA confirmed the role that it plays in the regulation of CYP46A1, as well as the production of 24-OHC and Aβ. In addition, this effect was stronger in the A type LincRNA than in the G type LincRNA. Results from dual luciferase assays show that LincRNA inhibited the activity of the CYP46A1 gene promoter. This study indicates a possible novel role of LincRNA and provides a new way to look into the relationship between CYP46A1 polymorphism and AD pathology. This may identify a novel pathway through which to explore AD therapy.https://www.frontiersin.org/article/10.3389/fnagi.2019.00381/fullCYP46A1long intronic non-coding RNA24-OHCamyloid βAlzheimer’s disease |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Yang Chen Hui-Yun Li Fan Zeng Le Chen Fa-Ying Zhou Ze-Yan Peng Hai Yang Hua-Dong Zhou Yan-Jiang Wang Ling Li |
spellingShingle |
Yang Chen Hui-Yun Li Fan Zeng Le Chen Fa-Ying Zhou Ze-Yan Peng Hai Yang Hua-Dong Zhou Yan-Jiang Wang Ling Li LincRNA Plays a Role in the Effect of CYP46A1 Polymorphism in Alzheimer’s Disease – Related Pathology Frontiers in Aging Neuroscience CYP46A1 long intronic non-coding RNA 24-OHC amyloid β Alzheimer’s disease |
author_facet |
Yang Chen Hui-Yun Li Fan Zeng Le Chen Fa-Ying Zhou Ze-Yan Peng Hai Yang Hua-Dong Zhou Yan-Jiang Wang Ling Li |
author_sort |
Yang Chen |
title |
LincRNA Plays a Role in the Effect of CYP46A1 Polymorphism in Alzheimer’s Disease – Related Pathology |
title_short |
LincRNA Plays a Role in the Effect of CYP46A1 Polymorphism in Alzheimer’s Disease – Related Pathology |
title_full |
LincRNA Plays a Role in the Effect of CYP46A1 Polymorphism in Alzheimer’s Disease – Related Pathology |
title_fullStr |
LincRNA Plays a Role in the Effect of CYP46A1 Polymorphism in Alzheimer’s Disease – Related Pathology |
title_full_unstemmed |
LincRNA Plays a Role in the Effect of CYP46A1 Polymorphism in Alzheimer’s Disease – Related Pathology |
title_sort |
lincrna plays a role in the effect of cyp46a1 polymorphism in alzheimer’s disease – related pathology |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Aging Neuroscience |
issn |
1663-4365 |
publishDate |
2020-01-01 |
description |
Polymorphism of the cholesterol-24S-hydroxylase (CYP46A1) gene is thought to be a risk factor for Alzheimer’s disease (AD). A single nucleotide polymorphism (T/C) in intron 2, rs754203, has been confirmed to be implicated in AD. Rs754203 is located in the long intronic non-coding RNA (LincRNA) sequence, which has previously been shown to be involved in the pathology of many diseases. Thus, the present study aimed to investigate the role of LincRNA in the CYP46A1 gene expression and related AD pathology. SH-SY5Y cells with overexpressed TT or CC genotype CYP46A1 were used. Through RT-PCR, Western blot and ELISA assays, we found that LincRNA can affect the CYP46A1 gene expression and the production of 24-OHC and Aβ. Overexpression of LincRNA can significantly inhibit CYP46A1 expression and 24-OHC production, as well as increasing the Aβ expression level. Silencing of LincRNA confirmed the role that it plays in the regulation of CYP46A1, as well as the production of 24-OHC and Aβ. In addition, this effect was stronger in the A type LincRNA than in the G type LincRNA. Results from dual luciferase assays show that LincRNA inhibited the activity of the CYP46A1 gene promoter. This study indicates a possible novel role of LincRNA and provides a new way to look into the relationship between CYP46A1 polymorphism and AD pathology. This may identify a novel pathway through which to explore AD therapy. |
topic |
CYP46A1 long intronic non-coding RNA 24-OHC amyloid β Alzheimer’s disease |
url |
https://www.frontiersin.org/article/10.3389/fnagi.2019.00381/full |
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