Systematic Review of miRNA as Biomarkers in Alzheimer’s Disease

Swarbrick, Samantha; Wragg, Nicholas M.; Ghosh, Sourav; Stolzing, Alexandra

doi:10.1007/s12035-019-1500-y

Cited by 273 publications

(232 citation statements)

References 122 publications

(101 reference statements)

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“…The structure, function and evolution of miRNAs including their expanding list of critical regulatory roles in CNS development and age-related human neurodegenerative diseases such as AD have been extensively reviewed and will not be dealt with further here [1,2,34,41,45,49,51,70,83,88]. Because miRNAs are relatively unstable in brain and retinal tissues with half-lives on the order of ~1-3 hrs, only significantly up-regulated miRNAs have been studied in short post-mortem interval (PMI) tissues of PMIs of 2-3 hrs or less; down-regulated miRNAs may simply be a consequence of the highly oxidative and pro-inflammatory degradative environment of actively degenerating neural tissues [11,59,67].…”

Section: Up-regulated Micrornas (Mirnas) and Down-regulation Of Essenmentioning

confidence: 99%

Lipopolysaccharide-stimulated, NF-kB-, miRNA-146a- and miRNA-155-mediated molecular-genetic communication between the human gastrointestinal tract microbiome and the brain

Alexandrov¹,

Zhai²,

Li³

et al. 2019

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Through the use of RNA sequencing, microRNA (miRNA) and messenger RNA (mRNA) microfluidic array analysis, LED Northern, Western and ELISA analysis and multiple bioinformatics algorithms we have discovered a novel route for pathogenic communication between the human gastrointestinal (GI)-tract microbiome and the brain. The evidence suggests that this pathogenic gut-brain circuit involves: (i) lipopolysaccharide (LPS) from the GI-tract resident enterotoxigenic Gram-negative bacteria Bacteroides fragilis (BF-LPS); (ii) LPS transit across the GI-tract barrier into the systemic circulation; (iii) transport of a highly pro-inflammatory systemic BF-LPS across the blood-brain barrier (BBB) into the brain-parenchyma and neuronal-cytoplasm; (iv) activation and signaling via the pro-inflammatory NF-kB (p50/p65) transcription-factor complex; (v) NF-kB-coupling and significant up-regulation of the inducible pro-inflammatory microRNA-146a (miRNA-146a) and microRNA-155 (miRNA-155); each containing multiple NF-kB DNA-binding and activation sites in their immediate promoters; and (vi) subsequent down-regulation of miRNA-146a-miRNA-155 regulated mRNA targets such as that encoding complement factor H (CFH), a soluble complement control glycoprotein and key repressor of the innate-immune response. Down-regulated CFH expression activates the complement-system, the major non-cellular component of the innate-immune system while propagating neuro-inflammation. Other GI-tract microbes and their highly complex pro-inflammatory exudates may contribute to this pathogenic GI-tract-brain pathway. We speculate that it may be significant that the first Gram-negative anaerobic bacterial species intensively studied as a potential contributor to the onset of Alzheimer's disease (AD), that being the bacillus Bacteroides fragilis appears to utilize damaged or leaky physiological barriers and an activated NF-kB (p50-p65)-pro-inflammatory miRNA-146a-miRNA-155 signaling circuit to convey microbiome-derived pathogenic signals into the brain.

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Section: Up-regulated Micrornas (Mirnas) and Down-regulation Of Essenmentioning

confidence: 99%

Lipopolysaccharide-stimulated, NF-kB-, miRNA-146a- and miRNA-155-mediated molecular-genetic communication between the human gastrointestinal tract microbiome and the brain

Alexandrov¹,

Zhai²,

Li³

et al. 2019

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“…Further, we analyzed theannotation network of KEGG pathways with P value less than 0.01 andfound that the total number of top10 C value miRNAs' target genesand their proportion in each region were larger than those of top10FC miRNAs, and top10 P value miRNAs. At the same time, we searcheda large number of literatures and got 14 skeletal muscle growthregulatory miRNAs [25][26][27][28][29][30][31][32][33][34][35][36][37][38], 6 Alzheimer's disease associatedmiRNAs [39][40][41][42], 7…”

Section: Discussionmentioning

confidence: 99%

Contribution Value：A Indicator for Measuring the Contribution of ncRNAs to Transcriptome

Gu¹,

Jin²,

Qi³

et al. 2020

Preprint

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Background：The expression difference multiple log2 FC and P value are often the main basis for screening ncRNA after high-throughput sequencing. However, the above two indicators can’t well reflect the regulatory effect of nonprotein coding RNA (ncRNA) on mRNA. Therefore, we propose a new indicator, Contribution value (C value), to characterize the contribution of ncRNAs to transcriptome transformation.Results：In this study, we analyzed multiple data sets from mice and humans. We take all differential expression mRNAs as a parent set and the GO and KEGG enrichment analysis were performed on it. C value can be simply regarded as the sum of the product of the richfactor of each ncRNA target genes participating in each term/pathway and the P value of that term/pathway obtained from the parent set. We found that C value was superior to log2 FC and P value in all operation results.Conclusions：We show that the C value, which takes into accounts the the KEGG pathways and GO terms involved in the development of the disease, provides a measure of another dimension compared with the log2FC and P value. These hidden interactions between ncRNAs and their target genes may provide more comprehensive analysis.

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“…Finally, expression of several circulating miRNAs was altered in blood from AD patients. Specifically, circulating miR-26b, miR-30e, miR-34a, miR-34c, miR-485, miR-200c, miR-210, miR-146a, and miR-125b were downregulated both in the brain and blood of AD patients compared to controls, suggesting a role for these miRNAs as potential markers for Alzheimer's disease [112]. Accordingly, expression of miR-125b is associated with the Mini Mental State Examination (MMSE), which is the most common tool for the evaluation of AD symptoms [113].…”

Section: Mirna: a Factor In Multifactorial Diseasesmentioning

confidence: 98%

miRNAs as Influencers of Cell–Cell Communication in Tumor Microenvironment

Conti

Varano

Simioni

et al. 2020

Cells

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microRNAs (miRNAs) are small noncoding RNAs that regulate gene expression at the posttranscriptional level, inducing the degradation of the target mRNA or translational repression. MiRNAs are involved in the control of a multiplicity of biological processes, and their absence or altered expression has been associated with a variety of human diseases, including cancer. Recently, extracellular miRNAs (ECmiRNAs) have been described as mediators of intercellular communication in multiple contexts, including tumor microenvironment. Cancer cells cooperate with stromal cells and elements of the extracellular matrix (ECM) to establish a comfortable niche to grow, to evade the immune system, and to expand. Within the tumor microenvironment, cells release ECmiRNAs and other factors in order to influence and hijack the physiological processes of surrounding cells, fostering tumor progression. Here, we discuss the role of miRNAs in the pathogenesis of multicomplex diseases, such as Alzheimer’s disease, obesity, and cancer, focusing on the contribution of both intracellular miRNAs, and of released ECmiRNAs in the establishment and development of cancer niche. We also review growing evidence suggesting the use of miRNAs as novel targets or potential tools for therapeutic applications.

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Systematic Review of miRNA as Biomarkers in Alzheimer’s Disease

Cited by 273 publications

References 122 publications

Lipopolysaccharide-stimulated, NF-kB-, miRNA-146a- and miRNA-155-mediated molecular-genetic communication between the human gastrointestinal tract microbiome and the brain

Lipopolysaccharide-stimulated, NF-kB-, miRNA-146a- and miRNA-155-mediated molecular-genetic communication between the human gastrointestinal tract microbiome and the brain

Contribution Value：A Indicator for Measuring the Contribution of ncRNAs to Transcriptome

miRNAs as Influencers of Cell–Cell Communication in Tumor Microenvironment

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