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Circular RNA (circRNA) in Alzheimer’s disease (AD)
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GENERAL COMMENTARY article Front. Genet., 31 December 2013 | https://doi.org/10.3389/fgene.2013.00307
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![Figure 1 (A) Detection of circRNA for miRNA-7 (ciRS-7) in sporadic Alzheimer's disease (AD) and age-matched control hippocampal CA1 [control (C) N = 4; AD (A) N = 6]; the single upper ciRS-7 (~1400 nt) band contains ~70 selectively conserved miRNA-7 binding sites as previously described (Hansen et al., 2013); a lower 28S RNA served as an internal loading control; all samples depleted of rRNA were treated with 50 units of RNaseR prior to electrophoresis RNaseR is a processive, Mg++-dependent hydrolytic exoribonuclease that degrades linear but not circular RNA; see Hansen et al. (2013); predicted circular transcripts consistently resisted an RNaseR challenge; 30 ug total AD and control hippocampal CA1 RNA was separated on agarose gels, transferred and probed with biotinylated or radiolabeled miRNA-7 probes as previously described (Colangelo et al., 2002; Hansen et al., 2013); detection was performed using a nonisotopic BrightStar BioDetect Kit (Ambion, Austin, TX; detection limit ~100 fg) or by standard autoradiography (Lukiw et al., 1992); (B) AD ciRS-7 is significantly reduced to about 0.18-fold of control (con) in a study of 20 control and AD (AD) hippocampal CA1 samples; this implicates loss of miRNA-7 sponge effects, an ambient up-regulation of miRNA-7 (as is observed), and down-regulation of a family of miRNA-7-sensitive mRNAs in the sporadic AD brain; other circRNAs may be involved; there were no significant differences between age for control or AD tissues [mean ± 1 standard deviation (SD) = 75.4 ± 8.3 year vs. 77.5 ± 7.6 year]; all AD cases were for moderate-to-advanced stages of AD; all post-mortem intervals were 2.1 h or less (Colangelo et al., 2002); there were no significant differences in age, ApoE allele status, RNA quality (all RIN values were 8.1–9.0) or yield between the control or AD groups (p > 0.05, ANOVA); a dashed horizontal line at 1.0 indicates homeostatic (control) ciRS-7 levels for ease of comparison; *p < 0.001 (ANOVA).](/paper-figures/a4706fbfe0d3497e8b376957eb291493/circular-rna-circrna-in-alzheimers-disease-ad-figure-1.jpg)
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“In addition, dysregulation of ciRS-7 has been found in zebrafish with an impaired midbrain [71] and in the hippocampus of AD patients [45].”
From Circular RNAs in depression: Biogenesis, function, expression, and therapeutic potential (2021) · cites this paper as [45]
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Circular RNAs are a large class of animal RNAs with regulatory potency
Memczak, S., Jens, M., Elefsinioti, A., Torti, F., Krueger, J., Rybak, A., Maier, L., Mackowiak, S. D., Gregersen, L. H., Munschauer, M., et al. (2013) · Nature · doi:10.1038/nature11928 · Cited by 7,990 · cited 1×
“Intrinsically resistant to exonucleolytic RNA decay, circRNAs appear to be enriched in mammalian brain tissues (Hansen et al., 2013; Memczak et al., 2013).”
BackgroundNatural RNA circles function as efficient microRNA sponges
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“Recently characterized, traditional methods of RNA detection and analysis requiring a free 5′ or 3′ ribonucleotide terminus may have significantly underestimated circRNA abundance and significance in eukaryotic cells (Salzman et al., 2012; Wilusz and Sharp, 2013; unpublished observations).”
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“…or AD groups (p > 0.05, ANOVA); a dashed horizontal line at 1.0 indicates homeostatic (control) ciRS-7 levels for ease of comparison; ∗p < 0.001 (ANOVA). contribute to the down-regulation of selective miRNA-7-sensitive messenger RNA (mRNA) targets (Cogswell et al., 2008; unpublished observations).”
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“Recently characterized, traditional methods of RNA detection and analysis requiring a free 5′ or 3′ ribonucleotide terminus may have significantly underestimated circRNA abundance and significance in eukaryotic cells (Salzman et al., 2012; Wilusz and Sharp, 2013; unpublished observations).”
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“…systems” and ambient up-regulation of specific inducible miRNAs may help explain the widely observed, generalized and progressive down-regulation of gene expression that is characteristic of the sporadic AD brain (Loring et al., 2001; Colangelo et al., 2002; Ginsberg et al., 2012; Lukiw, 2013).”
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“, 2013); detection was performed using a nonisotopic BrightStar BioDetect Kit (Ambion, Austin, TX; detection limit ∼100 fg) or by standard autoradiography (Lukiw et al., 1992); (B) AD ciRS-7 is significantly reduced to about 0.”
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“…but are also associated with a circRNA for miRNA-7 (ciRS-7), in the same tissues; ciRS-7 contains multiple, tandem anti-miRNA-7 sequences (Burmistrova et al., 2007; Hansen et al., 2013; Lukiw et al., 2013). ciRS-7 thereby acts as a kind of endogenous, competing, anti-complementary miRNA…”
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“…in the nervous system, these molecules play crucial roles in neurological diseases, including Alzheimer’s disease (AD), Parkinson’s disease (PD), and immune-mediated demyelinating diseases (Chen et al. 2021; Ghosal et al. 2013; Li et al. 2021; Lukiw 2013; Mehta et al. 2020; Zhao et al. 2016).”
Circular RNAs: Epigenetic regulators of PTEN expression and function in cancer
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“CircRNA is associated with a variety of chronic diseases, such as lung cancer, Alzheimer’s disease, diabetes, cardiovascular disease and other [10, 11].”
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Presence of Alzheimer's disease variants in circular RNA of PSEN1 and PSEN2
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“Universal circRNAs expression alterations have been identified in various diseases, including cancer [31], Alzheimer’s disease [32] and type 2 diabetes [33].”
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“…neurodegenerative and neuropsychiatric disorders, and exhibit dynamic regulation across many different cell-types, developmental stages, and neural activity (Jeck et al., 2013; Knupp & Miura, 2018; Lukiw, 2013; Rybak-Wolf et al., 2015; Wang et al., 2018; You et al., 2015; Zimmerman et al., 2020).”
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“CircRNA is a non-coding RNA (ncRNA) that is widely present in organisms and closely related to many diseases [17-20].”
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“In AD, differences of CDR1as expression levels have been observed in the 92 hippocampus (29, 30), one of the most vulnerable brain regions to tau deposition.”
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“…2020b), and circRNAs also have various biological functions and are involved in the pathogenesis of Alzheimer’s disease, rectal cancer, depression, ischemia/reperfusion injury and other diseases (Chen et al, 2020; Li et al, 2018b; Lukiw, 2013; Ma et al, 2018; Zhang et al, 2020; Zhou & Yu, 2017).”
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Analysis of serum CircRNA in related to gastric cancerPreprint
Chen, G., Su, Y. Y., Gong, H., Li, L., Zhang, Z., Wang, F., Nie, P., Ma, G.-G., Wang, X., Li, C., et al. (2020) · doi:10.21203/rs.2.16160/v2
Metadata
- Authors
- Lukiw, W. J.
- Affiliations
- Louisiana State University (US)
- Corresponding author
- Lukiw, Walter J.
- ORCID
- Lukiw, Walter J.
- Venue
- Frontiers in Genetics
- Publisher
- Frontiers Media SA
- Published
- 2013
- Volume
- 4
- Pages
- 307-307
- ISSN
- 1664-8021 (ISSN-L)
- PMC
- PMC3875874
- OpenAlex
- W2095799789
- Cited by
- 636
- References
- 14
- Citations by year
- 2026: 9 · 2025: 12 · 2024: 25 · 2023: 48 · 2022: 57 · 2021: 85 · 2020: 103 · 2019: 88 · 2018: 89 · 2017: 66 · 2016: 32 · 2015: 14 · 2014: 6
- FWCI
- 7.76
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by
- Locations
- Frontiers in Genetics (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Instytut Medycyny Doswiadczalnej i Klinicznej im. M. Mossakowskiego, Polskiej Akademii Nauk
- National Institute on Aging (AG038834, NIA AG038834, R01AG038834)
- National Eye Institute (NEI-EY-006311, R01EY006311, EY-006311)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Circular RNAs in diseases
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Keywords
- circular RNA, Alzheimer's disease, non-coding RNA, RNA circularization
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