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阿尔茨海默病患者海马组织中长链非编码 RNA 的差异表达谱及其相关共表达和竞争内源性 RNA 网络的综合分析。

Comprehensive Analysis of Differential Expression Profiles of Long Noncoding RNAs with Associated Co-expression and Competing Endogenous RNA Networks in the Hippocampus of Patients with Alzheimer's Disease.

机构信息

Department of Anesthesiology, Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital, Chengdu,China.

Department of Radiology, Chengdu Pidu District Hospital of traditional Chinese Medicine, Chengdu,China.

出版信息

Curr Alzheimer Res. 2021;18(11):884-899. doi: 10.2174/1567205018666211202143449.

DOI:10.2174/1567205018666211202143449
PMID:34856901
Abstract

BACKGROUND

Alzheimer's disease (AD) is still one of the major threats to human health. Although a satisfactory treatment for AD has not yet been discovered, it is necessary to continue to search for novel approaches to deal with this insidious and debilitating disease. Although numerous studies have shown that long non-coding RNA (lncRNA) occupy a significant role in a variety of diseases, their roles in AD remain unclear.

OBJECTIVE

Using data analysis to explore the role of lncRNA in the course of AD, to further our understanding of AD, and to look forward to finding a new breakthrough for the treatment of AD.

METHODS

We downloaded and screened expression data of the hippocampal regions of patients with AD from the Gene Expression Omnibus database. We generated lncRNA-miRNA-mRNA networks based on the competing endogenous RNA (ceRNA) hypothesis, and according to gene expression level, we constructed a coding-noncoding co-expression (CNC) network and then executed cis- and trans-regulation analyses.

RESULTS

Through comprehensive and systematic analyses, we found that lncRNAs MALAT1, OIP5-AS1, LINC00657, and lnc-NUMB-1 regulated the expression of the key AD pathogenic genes APP, PSEN1, BACE1; and that these lncRNAs may promote the distribution of β-amyloid (Aβ protein) in the brain through exosomes. In addition, lncRNAs were found to adjust viral transcriptional expression, thereby further supporting viral pathogenesis for AD.

CONCLUSION

The lncRNAs MALAT1, OIP5-AS1, LINC00657, and lnc-NUMB-1 that are present in the hippocampus of AD patients exert an important influence on the development of this disease.

摘要

背景

阿尔茨海默病(AD)仍然是人类健康的主要威胁之一。尽管尚未发现治疗 AD 的满意方法,但仍有必要继续寻找新的方法来应对这种隐匿和使人虚弱的疾病。尽管许多研究表明长链非编码 RNA(lncRNA)在各种疾病中具有重要作用,但它们在 AD 中的作用尚不清楚。

目的

使用数据分析探讨 lncRNA 在 AD 发病过程中的作用,进一步了解 AD,并期待为 AD 的治疗找到新的突破点。

方法

我们从基因表达综合数据库(Gene Expression Omnibus database)中下载并筛选了 AD 患者海马区的表达数据。我们基于竞争内源性 RNA(ceRNA)假说构建了 lncRNA-miRNA-mRNA 网络,并根据基因表达水平构建了编码-非编码共表达(CNC)网络,然后进行顺式和反式调控分析。

结果

通过全面系统的分析,我们发现 lncRNA MALAT1、OIP5-AS1、LINC00657 和 lnc-NUMB-1 调节 AD 关键致病基因 APP、PSEN1、BACE1 的表达;并且这些 lncRNA 可能通过外泌体促进β-淀粉样蛋白(Aβ 蛋白)在大脑中的分布。此外,发现 lncRNA 可以调节病毒转录表达,从而进一步支持 AD 的病毒发病机制。

结论

AD 患者海马体中存在的 lncRNA MALAT1、OIP5-AS1、LINC00657 和 lnc-NUMB-1 对疾病的发展有重要影响。

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