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Identification of let-7f and miR-338 as plasma-based biomarkers for sporadic amyotrophic lateral sclerosis using meta-analysis and empirical validation.
Sci Rep. 2022 01 26; 12(1):1373.SR

Abstract

Amyotrophic lateral sclerosis (ALS) is a lethal neurodegenerative disease that in most cases occurs sporadic (sALS). The disease is not curable, and its pathogenesis mechanisms are not well understood yet. Given the intricacy of underlying molecular interactions and heterogeneity of ALS, the discovery of molecules contributing to disease onset and progression will open a new avenue for advancement in early diagnosis and therapeutic intervention. Here we conducted a meta-analysis of 12 circulating miRNA profiling studies using the robust rank aggregation (RRA) method, followed by enrichment analysis and experimental verification. We identified miR-451a and let-7f-5p as meta-signature miRNAs whose targets are involved in critical pathogenic pathways underlying ALS, including 'FoxO signaling pathway', 'MAPK signaling pathway', and 'apoptosis'. A systematic review of 7 circulating gene profiling studies elucidated that 241 genes up-regulated in sALS circulation with concomitant being targets of the meta-signature miRNAs. Protein-protein interaction (PPI) network analysis of the candidate targets using MCODE algorithm revealed the main subcluster is involved in multiple cascades eventually leads apoptosis, including 'positive regulation of neuron apoptosis. Besides, we validated the meta-analysis results using RT-qPCR. Indeed, relative expression analysis verified let-7f-5p and miR-338-3p as significantly down-regulated and up-regulated biomarkers in the plasma of sALS patients, respectively. Receiver operating characteristic (ROC) analysis also highlighted the let-7f-5p and miR-338-3p potential as robustness plasma biomarkers for diagnosis and potential therapeutic targets of sALS disease.

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Authors+Show Affiliations

Daneshafrooz N
Cellular and Molecular Research Center, Department of Neuroscience, Faculty of Advanced Technologies in Medicine, Iran University of Medical Science, Tehran, Iran.
Joghataei MT
Cellular and Molecular Research Center, Department of Neuroscience, Faculty of Advanced Technologies in Medicine, Iran University of Medical Science, Tehran, Iran.
Mehdizadeh M
Reproductive Sciences and Technology Research Center, Department of Anatomy, School of Medicine, Iran University of Medical Science, Tehran, Iran.
Alavi A
Genetics Research Center, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran.
Barati M
Department of Medical Biotechnology, Faculty of Allied Medicine, Iran University of Medical Science, Tehran, Iran.
Panahi B
Department of Genomics, Branch for Northwest & West Region, Agricultural Biotechnology Research Institute of Iran (ABRII), Agricultural Research, Education and Extension Organization (AREEO), Tabriz, Iran.
Teimourian S
Department of Medical Genetics, School of Medicine, Iran University of Medical Science, Tehran, Iran.
Zamani B
Department of Neurology, Firoozgar Hospital, School of Medicine, Iran University of Medical Science, Tehran, Iran. zamaniba3@gmail.com.

MeSH

AlgorithmsAmyotrophic Lateral SclerosisBiomarkersCirculating MicroRNADown-RegulationEmpirical ResearchGene Expression ProfilingHigh-Throughput Nucleotide SequencingHumansMicroRNAsProtein Interaction MapsROC CurveReal-Time Polymerase Chain ReactionReverse Transcriptase Polymerase Chain ReactionTranscriptomeUp-Regulation

Pub Type(s)

Journal Article
Meta-Analysis
Research Support, Non-U.S. Gov't
Systematic Review

Language

eng

PubMed ID

35082326

Citation

Daneshafrooz, Narges, et al. "Identification of Let-7f and miR-338 as Plasma-based Biomarkers for Sporadic Amyotrophic Lateral Sclerosis Using Meta-analysis and Empirical Validation." Scientific Reports, vol. 12, no. 1, 2022, p. 1373.
Daneshafrooz N, Joghataei MT, Mehdizadeh M, et al. Identification of let-7f and miR-338 as plasma-based biomarkers for sporadic amyotrophic lateral sclerosis using meta-analysis and empirical validation. Sci Rep. 2022;12(1):1373.
Daneshafrooz, N., Joghataei, M. T., Mehdizadeh, M., Alavi, A., Barati, M., Panahi, B., Teimourian, S., & Zamani, B. (2022). Identification of let-7f and miR-338 as plasma-based biomarkers for sporadic amyotrophic lateral sclerosis using meta-analysis and empirical validation. Scientific Reports, 12(1), 1373. https://doi.org/10.1038/s41598-022-05067-4
Daneshafrooz N, et al. Identification of Let-7f and miR-338 as Plasma-based Biomarkers for Sporadic Amyotrophic Lateral Sclerosis Using Meta-analysis and Empirical Validation. Sci Rep. 2022 01 26;12(1):1373. PubMed PMID: 35082326.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Identification of let-7f and miR-338 as plasma-based biomarkers for sporadic amyotrophic lateral sclerosis using meta-analysis and empirical validation. AU - Daneshafrooz,Narges, AU - Joghataei,Mohammad Taghi, AU - Mehdizadeh,Mehdi, AU - Alavi,Afagh, AU - Barati,Mahmood, AU - Panahi,Bahman, AU - Teimourian,Shahram, AU - Zamani,Babak, Y1 - 2022/01/26/ PY - 2021/05/19/received PY - 2022/01/06/accepted PY - 2022/1/27/entrez PY - 2022/1/28/pubmed PY - 2022/3/8/medline SP - 1373 EP - 1373 JF - Scientific reports JO - Sci Rep VL - 12 IS - 1 N2 - Amyotrophic lateral sclerosis (ALS) is a lethal neurodegenerative disease that in most cases occurs sporadic (sALS). The disease is not curable, and its pathogenesis mechanisms are not well understood yet. Given the intricacy of underlying molecular interactions and heterogeneity of ALS, the discovery of molecules contributing to disease onset and progression will open a new avenue for advancement in early diagnosis and therapeutic intervention. Here we conducted a meta-analysis of 12 circulating miRNA profiling studies using the robust rank aggregation (RRA) method, followed by enrichment analysis and experimental verification. We identified miR-451a and let-7f-5p as meta-signature miRNAs whose targets are involved in critical pathogenic pathways underlying ALS, including 'FoxO signaling pathway', 'MAPK signaling pathway', and 'apoptosis'. A systematic review of 7 circulating gene profiling studies elucidated that 241 genes up-regulated in sALS circulation with concomitant being targets of the meta-signature miRNAs. Protein-protein interaction (PPI) network analysis of the candidate targets using MCODE algorithm revealed the main subcluster is involved in multiple cascades eventually leads apoptosis, including 'positive regulation of neuron apoptosis. Besides, we validated the meta-analysis results using RT-qPCR. Indeed, relative expression analysis verified let-7f-5p and miR-338-3p as significantly down-regulated and up-regulated biomarkers in the plasma of sALS patients, respectively. Receiver operating characteristic (ROC) analysis also highlighted the let-7f-5p and miR-338-3p potential as robustness plasma biomarkers for diagnosis and potential therapeutic targets of sALS disease. SN - 2045-2322 UR - https://www.unboundmedicine.com/medline/citation/35082326/Identification_of_let_7f_and_miR_338_as_plasma_based_biomarkers_for_sporadic_amyotrophic_lateral_sclerosis_using_meta_analysis_and_empirical_validation_ DB - PRIME DP - Unbound Medicine ER -