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Genome-wide profiling and predicted significance of post-mortem brain microRNA in Alzheimer's disease.
Mech Ageing Dev. 2020 10; 191:111352.MA

Abstract

BACKGROUND

MicroRNAs (miRNAs) emerged as regulatory elements, with up to 70 % of all miRNAs found in the brain, playing key roles in the onset of Alzheimer's disease (AD).

OBJECTIVE

to broadly assess the expression levels of miRNAs in post-mortem brain (PMB) samples of individuals deceased with or without AD.

METHODS

A high-throughput microarray platform was used to sketch miRNA samples isolated from superior and middle temporal gyrus of A+T+ AD cases, compared to samples from age- and sex-matched AD-devoid donors, all pulled from the University of São Paulo's Brain Biobank. The miRNAs identified by microarray were subjected to validation with specific qRT-PCR assays employing independent PMB samples.

RESULTS

The analyses yielded 6 miRNAs differentially expressed (miR-30e_3p; miR-365b_5p; miR-664_3p; miR-1202; miR-4286; miR-4449), and their interplay with specific AD-related genes and signaling pathways was explored using bioinformatics analyses (including the KEGG package, mirPath v.3). In the end, 3 miRNAs, 7 target genes and 11 pathways were found closely interrelated and implicated with the AD pathophysiology.

CONCLUSION

A dysregulation on a subset of these miRNAs appear to affect a range of genes (notably PTEN) and pathways (emphasis to PI3K-AKT) so to provide grounds for neuronal death by apoptotic signaling, autophagy and/or oxidative damage.

Links

Publisher Full Text (DOI)

Authors+Show Affiliations

Henriques AD
Federal University of Brasilia (UnB), Brasília, DF, Brazil.
Machado-Silva W
Federal University of Brasilia (UnB), Brasília, DF, Brazil.
Leite REP
State University of São Paulo (USP), São Paulo, SP, Brazil.
Suemoto CK
State University of São Paulo (USP), São Paulo, SP, Brazil.
Leite KRM
State University of São Paulo (USP), São Paulo, SP, Brazil.
Srougi M
State University of São Paulo (USP), São Paulo, SP, Brazil.
Pereira AC
State University of São Paulo (USP), São Paulo, SP, Brazil.
Jacob-Filho W
State University of São Paulo (USP), São Paulo, SP, Brazil.
Nóbrega OT
Federal University of Brasilia (UnB), Brasília, DF, Brazil; McGill University Health Center (MUHC), Montreal, QC, Canada. Electronic address: nobrega@pq.cnpq.br.
Brazilian Aging Brain Study Group
No affiliation info available

MeSH

AgedAged, 80 and overAlzheimer DiseaseFemaleGene Expression ProfilingGene Expression RegulationGenome-Wide Association StudyHumansMaleMicroRNAs

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

32920076

Citation

Henriques, Adriane D., et al. "Genome-wide Profiling and Predicted Significance of Post-mortem Brain microRNA in Alzheimer's Disease." Mechanisms of Ageing and Development, vol. 191, 2020, p. 111352.
Henriques AD, Machado-Silva W, Leite REP, et al. Genome-wide profiling and predicted significance of post-mortem brain microRNA in Alzheimer's disease. Mech Ageing Dev. 2020;191:111352.
Henriques, A. D., Machado-Silva, W., Leite, R. E. P., Suemoto, C. K., Leite, K. R. M., Srougi, M., Pereira, A. C., Jacob-Filho, W., & Nóbrega, O. T. (2020). Genome-wide profiling and predicted significance of post-mortem brain microRNA in Alzheimer's disease. Mechanisms of Ageing and Development, 191, 111352. https://doi.org/10.1016/j.mad.2020.111352
Henriques AD, et al. Genome-wide Profiling and Predicted Significance of Post-mortem Brain microRNA in Alzheimer's Disease. Mech Ageing Dev. 2020;191:111352. PubMed PMID: 32920076.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Genome-wide profiling and predicted significance of post-mortem brain microRNA in Alzheimer's disease. AU - Henriques,Adriane D, AU - Machado-Silva,Wilcelly, AU - Leite,Renata E P, AU - Suemoto,Claudia K, AU - Leite,Kátia R M, AU - Srougi,Miguel, AU - Pereira,Alexandre C, AU - Jacob-Filho,Wilson, AU - Nóbrega,Otávio T, AU - ,, Y1 - 2020/09/10/ PY - 2020/05/01/received PY - 2020/09/02/revised PY - 2020/09/04/accepted PY - 2020/9/14/pubmed PY - 2021/10/14/medline PY - 2020/9/13/entrez KW - Alzheimer’s disease KW - Array analysis KW - DIANA miRPath KW - microRNA SP - 111352 EP - 111352 JF - Mechanisms of ageing and development JO - Mech Ageing Dev VL - 191 N2 - BACKGROUND: MicroRNAs (miRNAs) emerged as regulatory elements, with up to 70 % of all miRNAs found in the brain, playing key roles in the onset of Alzheimer's disease (AD). OBJECTIVE: to broadly assess the expression levels of miRNAs in post-mortem brain (PMB) samples of individuals deceased with or without AD. METHODS: A high-throughput microarray platform was used to sketch miRNA samples isolated from superior and middle temporal gyrus of A+T+ AD cases, compared to samples from age- and sex-matched AD-devoid donors, all pulled from the University of São Paulo's Brain Biobank. The miRNAs identified by microarray were subjected to validation with specific qRT-PCR assays employing independent PMB samples. RESULTS: The analyses yielded 6 miRNAs differentially expressed (miR-30e_3p; miR-365b_5p; miR-664_3p; miR-1202; miR-4286; miR-4449), and their interplay with specific AD-related genes and signaling pathways was explored using bioinformatics analyses (including the KEGG package, mirPath v.3). In the end, 3 miRNAs, 7 target genes and 11 pathways were found closely interrelated and implicated with the AD pathophysiology. CONCLUSION: A dysregulation on a subset of these miRNAs appear to affect a range of genes (notably PTEN) and pathways (emphasis to PI3K-AKT) so to provide grounds for neuronal death by apoptotic signaling, autophagy and/or oxidative damage. SN - 1872-6216 UR - https://www.unboundmedicine.com/medline/citation/32920076/Genome_wide_profiling_and_predicted_significance_of_post_mortem_brain_microRNA_in_Alzheimer's_disease_ DB - PRIME DP - Unbound Medicine ER -