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.
Highlights
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]
We investtigated the hippocampal expression patterns of dysregulated long non-coding RNAs (lncRNAs) in a rat model of AD using microarray analysis and demonstrated that lncRNAs contributed to the pathogenesis of AD [6]
Lukiw et al [12, 13] demonstrated that circRNA-7(ciRS-7) acted as a natural miRNA sponge for miRNA-7 and regulated the expression of ubiquitin-conjugating enzyme E2A (UBE2A) and the epidermal growth factor receptor (EGFR) in sporadic AD hippocampal brain
Summary
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]. Unlike linear RNA, circRNA is formed with covalently closed continuous loops without 5’-3’ polarity and a poly(A) tail, and might function as microRNA sponges to modulate the expression of parental genes through the competing endogenous RNA (ceRNA) network [10]. Recent studies have provided evidence that the circRNA-associated ceRNA network may play a crucial role in many disease processes, including AD [11]. Lukiw et al [12, 13] demonstrated that circRNA-7(ciRS-7) acted as a natural miRNA sponge for miRNA-7 and regulated the expression of ubiquitin-conjugating enzyme E2A (UBE2A) and the epidermal growth factor receptor (EGFR) in sporadic AD hippocampal brain. Zhang et al [14] characterized circRNA-associated-ceRNA networks in the cerebral cortex of senescence-accelerated mouse prone 8(SAMP8). The potential role of circRNAs in the pathogenesis of AD is still in its infancy and has yet to be characterized, the role of circRNA-associated-ceRNA networks in the hippocampus of AD
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
