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Mol Neurobiol. 2019 Sep;56(9):6106-6120. doi: 10.1007/s12035-019-1480-y. Epub 2019 Feb 5.

Wide Profiling of Circulating MicroRNAs in Spinocerebellar Ataxia Type 7.

Author information

1
Laboratory of Genomic Medicine, Department of Genetics, National Rehabilitation Institute (INR-LGII), Calz. México-Xochimilco No. 289, Col. Arenal Guadalupe, 14389, Ciudad de México (CDMX), Mexico.
2
Department of Genetics and Molecular Biology, Center of Research and Advanced Studies (CINVESTAV-IPN), Av. Instituto Politécnico Nacional No. 2508, Col. San Pedro Zacatenco, 07360, Ciudad de México (CDMX), Mexico.
3
Laboratory of Cancer Genomics, National Genomics Medicine Institute (INMEGEN), Mexico City, Mexico.
4
Molecular Targeting Unit, Department of Experimental Oncology and Molecular Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
5
Rehabilitation and Special Education Center of Veracruz (CRIS-DIF), Xalapa, Veracruz, Mexico.
6
Department of Genetics and Molecular Biology, Center of Research and Advanced Studies (CINVESTAV-IPN), Av. Instituto Politécnico Nacional No. 2508, Col. San Pedro Zacatenco, 07360, Ciudad de México (CDMX), Mexico. bcisnero@cinvestav.mx.
7
Laboratory of Genomic Medicine, Department of Genetics, National Rehabilitation Institute (INR-LGII), Calz. México-Xochimilco No. 289, Col. Arenal Guadalupe, 14389, Ciudad de México (CDMX), Mexico. maganasm@hotmail.com.

Abstract

Spinocerebellar ataxia type 7 (SCA7), a neurodegenerative disease characterized by cerebellar ataxia and retinal degeneration, is caused by a CAG repeat expansion in the ATXN7 gene coding region. Disease onset and progression are highly variable between patients, thus identification of specific/sensitive biomarkers that can improve the monitoring of disease progression is an immediate need. Because altered expression of circulating microRNAs (miRNAs) has been shown in various neurological diseases, they could be useful biomarkers for SCA7. In this study, we showed, to our knowledge for the first time, the expression profile of circulating miRNAs in SCA7. Using the TaqMan profiling low density array (TLDA), we found 71 differentially expressed miRNAs in the plasma of SCA7 patients, compared with healthy controls. The reliability of TLDA data was validated independently by quantitative real-time polymerase chain reaction in an independent cohort of patients and controls. We identified four validated miRNAs that possesses the diagnostic value to discriminate between healthy controls and patients (hsa-let-7a-5p, hsa-let7e-5p, hsa-miR-18a-5p, and hsa-miR-30b-5p). The target genes of these four miRNAs were significantly enriched in cellular processes that are relevant to central nervous system function, including Fas-mediated cell-death, heparansulfate biosynthesis, and soluble-N-ethylmaleimide-sensitive factor activating protein receptor pathways. Finally, we identify a signature of four miRNAs associated with disease severity that discriminate between early onset and adult onset, highlighting their potential utility to surveillance disease progression. In summary, circulating miRNAs might provide accessible biomarkers for disease stage and progression and help to identify novel cellular processes involved in SCA7.

KEYWORDS:

Plasma biomarker; PolyQ disease; Spinocerebellar ataxia type 7; miRNAs

PMID:
30721448
DOI:
10.1007/s12035-019-1480-y
[Indexed for MEDLINE]

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