Abstract
Long non-coding RNAs (lncRNAs), as important ncRNA regulators, play crucial roles in the regulation of various biological processes, and their aberrant expression is related to the occurrence and development of diseases, which is gradually validated by more and more studies. Alzheimer’s disease (AD) is a chronic neurodegenerative disease that often develops slowly and gradually deteriorates over time. However, which functions the lncRNAs perform in AD are almost unknown. In this study, we performed transcriptome analysis in AD, containing 12,892 known lncRNAs and 19,053 protein-coding genes (PCGs). Further, 14 down-regulated and 39 up-regulated lncRNAs were identified, compared with normal brain samples, which indicated that these lncRNAs might play critical roles in the pathogenesis of AD. In addition, 19 down-regulated and 28 up-regulated PCGs were also detected. Using the differentially expressed lncRNAs and PCGs through the WGCNA method, an lncRNA–mRNA co-expressed network was constructed. The results showed that lncRNAs RP3-522J7, MIR3180-2, and MIR3180-3 were frequently co-expressed with known AD risk PCGs. Interestingly, PCGs in the network are significantly enriched in brain- or AD-related biological functions, including the brain renin–angiotensin system, cell adhesion, neuroprotective role of THOP1 in AD, and so on. Furthermore, it was shown that 18 lncRNAs and 7 PCGs were highly expressed in normal brain tissue relative to other normal tissue types, suggesting their potential as diagnostic markers of AD, especially RP3-522J7, MIR3180-2, MIR3180-3, and CTA-929C8. In total, our study identified a compendium of AD-related dysregulated lncRNAs and characterized the corresponding biological functions of these lncRNAs in AD, which will be helpful to understand the molecular basis and pathogenesis of AD.
Highlights
Alzheimer’s disease (AD) is an insidious progressive neurodegenerative disease, which is affected by many factors, including environmental factors and genetic and epigenetic variations (Toledo et al, 2015), but there is no doubt that aging is the biggest risk factor (Kold-Christensen and Johannsen, 2019)
RNA-seq data of AD cortex tissue was obtained to identify the differentially expressed long non-coding RNAs (lncRNAs) and protein-coding genes (PCGs); we established a co-expression network which could be helpful to identify a list of candidate AD-related lncRNAs
The lncRNA–PCG co-expressed network was constructed by WGCNA and was enriched in the AD-associated biological processes, such as cell adhesion, brain renin–angiotensin system, neuroprotective role of THOP1 in AD, and so on
Summary
Alzheimer’s disease (AD) is an insidious progressive neurodegenerative disease, which is affected by many factors, including environmental factors and genetic and epigenetic variations (Toledo et al, 2015), but there is no doubt that aging is the biggest risk factor (Kold-Christensen and Johannsen, 2019). A considerable part of the human genome regions could transcribe as long non-coding RNAs (lncRNAs), a set of non-coding transcripts longer than 200 nt, which play important roles in various life activities, such as embryonic development, cell differentiation, aging, and complex diseases (Derrien et al, 2012; Rinn and Chang, 2012). As previous research has shown, due to the complex and transcriptional regulation mechanisms, lncRNAs could be focused on their roles in human complex diseases, including AD and cancers, to gain new insights into complex disease pathways, to identify biomarkers to improve diagnostic accuracy, and to examine the impact of treatment (Zhou et al, 2019). The role of lncRNAs in the pathogenesis and progression of certain human complex diseases remains unclear, AD.
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