Objective: 1.Identification of microRNAs from whole blood PBMCs of SCA2 patients by using NGS.
2.To check the exclusivity of miRNAs in SCA2, SCA1,SCA3,SCA12,HD,ALS,PD and MSA-C by using qRTPCR validation.
Background: The polyglutamine stretch extension in the ataxin-2 protein is the cause of spinocerebellar ataxia type-2 (SCA-2). The identity of the miRNAs seen in different neurodegenerative illnesses but not yet discovered in SCA2 [2,3,4] . We used NGS to identify the miRNAs and then validated the miRNAs that were most closely related with the major pathways.
Method: In smallRNA sequencing (NGS) based profiling of miRNAs, total SCA2 patients (N=7) and controls (N=7) were used to find differentially expressed miRNAs on Illumina Hiseq2500 platform. Differential expression of miRNAs analysis was performed using DESeq2 software.TargetScan, miRTarBase and miRPath V.3 version were utilized for pathway analysis.
Selected miRNAs were validated using qRT-PCR method on Roche Light Cycler 480 version in SCA2 (N=28 vs. controls N=28).Also validated in other neurodegenerative diseases (N=10 vs. controls N=10) in SCA1, SCA3,PD (N=10) and MSA-C. The differential expression of qRT-PCR analysis was done by using unpaired t test.
Results: NGS analysis showed in between total 6 up & down regulated miRNAs in patient versus controls, 2down-regulated miRNAs (hsa-mir-451a***and hsa-mir-451b***) found to be most significant miRNAs at ≥2-fold change expression level at p<0.05 . Hierarchical clustering of all identified miRNAs in all 14 samples is shown in figure (Figure1).
The miRNA family hsa-miR-451 targets the genes HIPK2, NR4A3, VEGFA, RAB10,RAB18 and ATXN2 whic involved in neurodegeneration pathways. .qRT-PCR validation results showing that hsa-miR-451a and 451b significantly down regulated in SCA2 and also down regulated in other neurodegenerative diseases like in SCA1,SCA12,HD,ALS,PD & MSA-C except SCA3 (Table1 & Figure2).
Conclusion: The members of hsa-miR-451family were shown to be considerably downregulated in SCA2, SCA1, SCA12, HD, ALS, MSA-C and PD. The most significant factor is that miRNA hsa-miR-451protect the mitochondrial function by guarding against oxidative stress. In degenerative pathways, downregulation or deletion of hsa-miR-451 plays a functional role [5,6,7].
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Daniel Hamberger, Ute Schaefer, Silke Patz (2018) MicroRNA451a overexpression induces accelerated neuronal differentiation of Ntera2/D1 cells and ablation affects
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To cite this abstract in AMA style:R. Singh, V. Swarup, I. Ahmad, V. Anand, I. Singh, M. Faruq, A. Srivastava. The neuroprotective miRNA family hsa-miR-451 has a distinctive pattern of downregulation in neurodegenerative diseases. [abstract]. Mov Disord. 2023; 38 (suppl 1). https://www.mdsabstracts.org/abstract/the-neuroprotective-mirna-family-hsa-mir-451-has-a-distinctive-pattern-of-downregulation-in-neurodegenerative-diseases/. Accessed September 23, 2023.
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