Differential microRNA expression in the SH-SY5Y human cell model as potential biomarkers for Huntington’s disease
Belkozhayev A. Niyazova R. Kamal M.A. Ivashchenko A. Sharipov K. Wilson C.M.
2024Frontiers Media SA
Frontiers in Cellular Neuroscience
2024#18
Huntington’s disease (HD) is caused by an expansion of CAG trinucleotide repeat in the HTT gene; the exact pathogenesis of HD currently remains unclear. One of the promising directions in the study of HDs is to determine the molecular mechanism underlying the development and role of microRNAs (miRNAs). This study aimed to identify the profile of miRNAs in an HD human cell line model as diagnostic biomarkers for HD. To study HD, the human SH-SY5Y HD cell model is based on the expression of two different forms: pEGFP-Q23 and pEGFP-Q74 of HTT. The expression of Htt protein was confirmed using aggregation assays combined with immunofluorescence and Western blotting methods. miRNA levels were measured in SH-SY5Y neuronal cell model samples stably expressing Q23 and Q74 using the extraction-free HTG EdgeSeq protocol. A total of 2083 miRNAs were detected, and 354 (top 18 miRNAs) miRNAs were significantly differentially expressed (DE) (p < 0.05) in Q23 and Q74 cell lines. A majority of the miRNAs were downregulated in the HD cell model. Moreover, we revealed that six DE miRNAs target seven genes (ATN1, GEMIN4, EFNA5, CSMD2, CREBBP, ATXN1, and B3GNT) that play important roles in neurodegenerative disorders and showed significant expression differences in mutant Htt (Q74) when compared to wild-type Htt (Q23) using RT-qPCR (p < 0.05 and 0.01). We demonstrated the most important DE miRNA-mRNA profiles, interaction binding sites, and their related pathways in HD using experimental and bioinformatics methods. This will allow the development of novel diagnostic strategies and provide alternative therapeutic routes for treating HD. Copyright
biomarker , Huntington’s disease , miRNA , nucleotide repeats , target genes
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Life Sciences Industry Liaison Lab, School of Psychology and Life Sciences, Canterbury Christ Church University, Sandwich, United Kingdom
M.A. Aitkhozhin Institute of Molecular Biology and Biochemistry, Almaty, Kazakhstan
Department of Chemical and Biochemical Engineering, Geology and Oil-Gas Business Institute Named after K. Turyssov, Satbayev University, Almaty, Kazakhstan
Faculty of Biology and Biotechnology, Al-Farabi Kazakh National University, Almaty, Kazakhstan
Novel Global Community Educational Foundation, Hebersham, NSW, Australia
Center for High Altitude Medicine, Institutes for Systems Genetics, West China School of Nursing, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu, China
King Fahd Medical Research Center, King Abdulaziz University, Jeddah, Saudi Arabia
Department of Pharmacy, Faculty of Health and Life Sciences, Daffodil International University, Dhaka, Bangladesh
Centre for Global Health Research, Saveetha Medical College and Hospital, Saveetha Institute of Medical and Technical Sciences, Chennai, India
Enzymoics, Hebersham, NSW, Australia
Center for Bioinformatics and Nanomedicine, Almaty, Kazakhstan
Department of Biochemistry, Asfendiyarov Kazakh National Medical University, Almaty, Kazakhstan
University of Liverpool, Liverpool, United Kingdom
Life Sciences Industry Liaison Lab
M.A. Aitkhozhin Institute of Molecular Biology and Biochemistry
Department of Chemical and Biochemical Engineering
Faculty of Biology and Biotechnology
Novel Global Community Educational Foundation
Center for High Altitude Medicine
King Fahd Medical Research Center
Department of Pharmacy
Centre for Global Health Research
Enzymoics
Center for Bioinformatics and Nanomedicine
Department of Biochemistry
University of Liverpool
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