Analysis of transcription factor- and ncRNA-mediated potential pathogenic gene modules in Alzheimer’s disease

Zou, Cuihua; Wang, Jie; Huang, Xiaohua; Jian, Chongdong; Zou, Donghua; Li, Xuebin

doi:10.18632/aging.102169

Cited by 15 publications

(14 citation statements)

References 37 publications

(37 reference statements)

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“…The Wnt dysfunction results in Aβ production and aggregation in vitro , which promotes AD [25]. Apoptosis was also found to be significantly associated with AD [26]. In our study, we found the Rap1 signaling pathway, MAPK signaling pathway and autophagy were associated with AD.…”

Section: Discussionsupporting

confidence: 51%

Identification of molecular correlations of RBM8A with autophagy in Alzheimer's disease

Zou

Huang

et al. 2019

Aging

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Our previous studies revealed RBM8A may play a role in various progressive neurological diseases. The present study aimed to explore the role of RBM8A in Alzheimer's disease (AD). RBM8A is significantly down-regulated in AD. Interestingly, 9186 differentially expressed genes are overlapped from comparisons of AD versus control and RBM8A-low versus RBM8A-high. Weight gene correlation analysis was performed and 9 functional modules were identified. Modules positively correlated with AD and RBM8A-low are significantly involved in the RAP1 signaling pathway, PI3K−AKT signaling pathway, hematopoietic cell lineage, autophagy and APELIN signaling pathway. Fifteen genes (RBM8A, RHBDF2, TNFRSF10B, ACP1, ANKRD39, CA10, CAMK4, CBLN4, LOC284214, NOVA1, PAK1, PPEF1, RGS4, TCEB1 and TMEM118) are identified as hub genes, and the hub gene-based LASSO model can accurately predict the occurrence of AD (AUC = 0.948). Moreover, the RBM8A-module-pathway network was constructed, and low expression of RBM8A down-regulates multiple module genes, including FIP200, Beclin 1, NRBF2, VPS15 and ATG12, which composes key complexes of autophagy. Thus, our study supports that low expression of RBM8A correlates with the decrease of the components of key complexes in autophagy, which could potentially contribute to pathophysiological changes of AD.

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Section: Discussionsupporting

confidence: 51%

Identification of molecular correlations of RBM8A with autophagy in Alzheimer's disease

Zou

Huang

et al. 2019

Aging

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“…So far, AD treatments are only palliative and delay the development of symptoms, without halting or reversing the disease. 7 …”

Section: Introductionmentioning

confidence: 99%

Gene Set Index Based on Different Modules May Help Differentiate the Mechanisms of Alzheimer’s Disease and Vascular Dementia

Zhou¹,

Chen²,

Chen³

et al. 2021

CIA

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Purpose Alzheimer’s disease (AD) and vascular dementia shared similar symptoms, the aim of the present study was to identify potential differences in the mechanisms underlying the two diseases. Materials and Methods The data set including AD, vascular dementia, and control samples was carried out gene differential expression analysis, weighted gene co-expression network analysis, functional enrichment, protein–protein interaction network construction, and least absolute shrinkage and selection operator analysis to reveal the differences in the mechanisms underlying the two diseases and potential diagnostic gene signature. Results We identified the gene modules related to AD or vascular dementia. Enrichment analysis of module genes and construction of a protein–protein interaction network suggested that the “brown” module may be involved in a chemokine pathway, the “blue” module may be involved in cortisol synthesis and secretion, and the “turquoise” module may be involved in cholinergic synapse transmission. The hub gene-based signature index may be a biomarker of AD and vascular dementia and may even differentiate the two diseases from each other with high area under curve. Conclusion Our results identified not only core pathways involved in both AD and vascular disease, but also their potentially specific pathways. We proposed the hub gene-based signature index may be useful for diagnosing AD and vascular dementia.

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“…Currently, the mainstay of AD treatment is the combination of daily life care from the carers or nurses of the patients and drug therapy, with the latter mainly including cholinesterase inhibitors and glutamate antagonists (5). However, ad remains a disease that cannot yet be cured, even though accumulating factors have been found to be useful in AD management; therefore, further efforts are required to explore the underlying mechanisms of ad pathogenesis (6)(7)(8). long non-coding rnas (lncrnas) are a category of noncoding rnas (ncrnas) that have almost no protein coding function and a length of >200 nucleotides (9).…”

Section: Introductionmentioning

confidence: 99%

Long non-coding RNA ANRIL knockdown suppresses apoptosis and pro-inflammatory cytokines while enhancing neurite outgrowth via binding microRNA-125a in a cellular model of Alzheimer's disease

Zhou

Qiu

et al. 2020

Mol Med Rep

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The present study aimed to investigate the effect of the long non-coding rna antisense non-coding rna in the inK4 locus (lnc-anril) knockdown on apoptosis, neurite outgrowth and inflammation based on a PC12 cellular alzheimer's disease (ad) model. a cellular ad model was constructed by treating nerve growth factor stimulated PC12 cells with amyloid β (aβ) 1-42 and then control knockdown plasmid and lnc-anril knockdown plasmid were transfected in the Pc12 cellular ad model as the Kd-negative control (nc) group or the ad-anril group respectively. Apoptosis, neurite outgrowth, pro-inflammatory cytokines and microrna (mir)-125a were assessed. rescue experiments were conducted by transfecting lnc-ANRIL knockdown plasmid and lnc-anril knockdown plasmid and mir-125a inhibitor in the PC12 cellular AD model as the KD-ANRIL group or Kd-anril + Kd-mir-125a group respectively. Following transfection, cell apoptosis deccreased while neurite outgrowth increased in the Kd-anril group compared with the Kd-nc group (all P<0.01). concerning inf lammation, tumor necrosis factor-α (TnF-α) and interleukin (il)-1β, il-6 and il-17 were decreased in the Kd-anril group compared with the Kd-nc group (all P<0.01). miR-125a was negatively regulated by lnc-ANRIL and therefore rescue experiments were subsequently conducted. in the rescue experiments, cell apoptosis was increased while total neurite outgrowth was inhibited in the Kd-anril + Kd-mir-125a group compared with the Kd-anril group (all P<0.01), and TnF-α, il-1β, il-6 and il-17 were increased in the Kd-anril + Kd-mir-125a group compared with the Kd-anril group (all P<0.01). a luciferase reporter assay demonstrated that lnc-ANRIL directly bound miR-125a. lnc-ANRIL knockdown suppressed cell apoptosis and inflammation while promoting neurite outgrowth via binding of miR-125a in AD.

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Analysis of transcription factor- and ncRNA-mediated potential pathogenic gene modules in Alzheimer’s disease

Cited by 15 publications

References 37 publications

Identification of molecular correlations of RBM8A with autophagy in Alzheimer's disease

Identification of molecular correlations of RBM8A with autophagy in Alzheimer's disease

Gene Set Index Based on Different Modules May Help Differentiate the Mechanisms of Alzheimer’s Disease and Vascular Dementia

Long non-coding RNA ANRIL knockdown suppresses apoptosis and pro-inflammatory cytokines while enhancing neurite outgrowth via binding microRNA-125a in a cellular model of Alzheimer's disease

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