miRNA analysis reveals novel dysregulated pathways in amyotrophic lateral sclerosis.

Autor:	Hur J; Department of Biomedical Sciences, University of North Dakota, Grand Forks, ND 58202, USA., Paez-Colasante X; Department of Neurology, University of Michigan, Ann Arbor, MI 48109, USA., Figueroa-Romero C; Department of Neurology, University of Michigan, Ann Arbor, MI 48109, USA.; NeuroNetwork for Emerging Therapies, University of Michigan, Ann Arbor, MI 48109, USA., Lo TW; Department of Chemical Engineering, University of Michigan, Ann Arbor, MI 48109, USA., Barmada SJ; Department of Neurology, University of Michigan, Ann Arbor, MI 48109, USA., Paulsen MT; Department of Radiation Oncology, University of Michigan, Ann Arbor, MI 48109, USA., Ljungman M; Department of Radiation Oncology, University of Michigan, Ann Arbor, MI 48109, USA.; Department of Internal Medicine, Division of Nephrology, University of Michigan, Ann Arbor, MI 48109, USA., Alakwaa FM; Department of Neurology, University of Michigan, Ann Arbor, MI 48109, USA., Savelieff MG; NeuroNetwork for Emerging Therapies, University of Michigan, Ann Arbor, MI 48109, USA., Goutman SA; Department of Neurology, University of Michigan, Ann Arbor, MI 48109, USA.; NeuroNetwork for Emerging Therapies, University of Michigan, Ann Arbor, MI 48109, USA., Feldman EL; Department of Neurology, University of Michigan, Ann Arbor, MI 48109, USA.; NeuroNetwork for Emerging Therapies, University of Michigan, Ann Arbor, MI 48109, USA.
Jazyk:	angličtina
Zdroj:	Human molecular genetics [Hum Mol Genet] 2023 Mar 06; Vol. 32 (6), pp. 934-947.
DOI:	10.1093/hmg/ddac250
Abstrakt:	Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease. Its complex pathogenesis and phenotypic heterogeneity hinder therapeutic development and early diagnosis. Altered RNA metabolism is a recurrent pathophysiologic theme, including distinct microRNA (miRNA) profiles in ALS tissues. We profiled miRNAs in accessible biosamples, including skin fibroblasts and whole blood and compared them in age- and sex-matched healthy controls versus ALS participants with and without repeat expansions to chromosome 9 open reading frame 72 (C9orf72; C9-ALS and nonC9-ALS), the most frequent ALS mutation. We identified unique and shared profiles of differential miRNA (DmiRNA) levels in each C9-ALS and nonC9-ALS tissues versus controls. Fibroblast DmiRNAs were validated by quantitative real-time PCR and their target mRNAs by 5-bromouridine and 5-bromouridine-chase sequencing. We also performed pathway analysis to infer biological meaning, revealing anticipated, tissue-specific pathways and pathways previously linked to ALS, as well as novel pathways that could inform future research directions. Overall, we report a comprehensive study of a miRNA profile dataset from C9-ALS and nonC9-ALS participants across two accessible biosamples, providing evidence of dysregulated miRNAs in ALS and possible targets of interest. Distinct miRNA patterns in accessible tissues may also be leveraged to distinguish ALS participants from healthy controls for earlier diagnosis. Future directions may look at potential correlations of miRNA profiles with clinical parameters. (© The Author(s) 2022. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)
Databáze:	MEDLINE
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