Research Article: Identifying circRNA-associated-ceRNA networks in the hippocampus of Aβ1-42-induced Alzheimer’s disease-like rats using microarray analysis

Date Published: April 27, 2018

Publisher: Impact Journals

Author(s): Zhe Wang, Panpan Xu, Biyue Chen, Zheyu Zhang, Chunhu Zhang, Qiong Zhan, Siqi Huang, Zi-an Xia, Weijun Peng.

http://doi.org/10.18632/aging.101427

Abstract

Alzheimer’s disease (AD) is the most common form of dementia worldwide. Accumulating evidence indicates that non-coding RNAs are strongly implicated in AD-associated pathophysiology. However, the role of these ncRNAs remains largely unknown. In the present study, we used microarray analysis technology to characterize the expression patterns of circular RNAs (circRNAs), microRNAs (miRNAs), and mRNAs in hippocampal tissue from Aβ1-42-induced AD model rats, to integrate interaction data and thus provide novel insights into the mechanisms underlying AD. A total of 555 circRNAs, 183 miRNAs and 319 mRNAs were identified to be significantly dysregulated (fold-change ≥ 2.0 and p-value < 0.05) in the hippocampus of AD rats. Quantitative real-time polymerase chain reaction (qRT-PCR) was then used to validate the expression of randomly-selected circRNAs, miRNAs and mRNAs. Next, GO and KEGG pathway analyses were performed to further investigate ncRNAs biological functions and potential mechanisms. In addition, we constructed circRNA-miRNA and competitive endogenous RNA (ceRNA) regulatory networks to determine functional interactions between ncRNAs and mRNAs. Our results suggest the involvement of different ncRNA expression patterns in the pathogenesis of AD. Our findings provide a novel perspective for further research into AD pathogenesis and might facilitate the development of novel therapeutics targeting ncRNAs.

Partial Text

Alzheimer’s disease (AD), the most common cause of dementia worldwide, is becoming more prevalent due to the aging population, and represents one of the grand challenges to health care systems [1]. Although substantial progress has been made in the identification of disease-related molecular and cellular processes over the last decade, the molecular mechanisms that underlie the pathogenesis of AD remain largely unknown [2], and none of the pharmacological treatments presently available for AD are able to stop or slow down the progression of this disease [3].Therefore, further investigation of the underlying disease mechanisms are urgently required in order to better understand AD and to facilitate the development of effective therapeutic strategies.

To the best of our knowledge, this is the first integrated microarray analysis of circRNA, miRNA and mRNA expression profiles in the hippocampus of Aβ1-42-induced AD model rats. With FC ≥ 2.0 and p-value < 0.05 thresholds, 444 up-regulated and 111 down-regulated circRNAs, 93 up-regulated and 90 down-regulated miRNAs, and 173 up-regulated and 146 down-regulated mRNAs showed significant differential expression between the AD and control groups. These transcripts are thought to be associated with the pathogenesis of AD. For instance, the S100A8 precedes Aβ plaque formation [17], IGFBP-2 drives AD neurodegeneration [18], miR-146a-5p facilitates neuroinflammation in AD pathogenesis [19], and miR-132-3p contributes to tau hyper-phosphorylation [20]. Our qRT-PCR validation showd that the qRT-PCR results and microarray data were consistent, indicating that the latter were reliable.   Source: http://doi.org/10.18632/aging.101427

 

Leave a Reply

Your email address will not be published.