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Aberrant Expression of Circulating MicroRNA Leads to the Dysregulation of Alpha-Synuclein and Other Pathogenic Genes in Parkinson’s Disease
A group of circulating microRNAs (miRNAs) have been implicated in the pathogenesis of Parkinson’s disease. However, a comprehensive study of the interactions between pathogenic miRNAs and their downstream Parkinson’s disease (PD)-related target genes has not been performed. Here, we identified the m...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8419519/ https://www.ncbi.nlm.nih.gov/pubmed/34497805 http://dx.doi.org/10.3389/fcell.2021.695007 |
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author | Cai, Meng Chai, Songshan Xiong, Tao Wei, Jun Mao, Weibing Zhu, Yasha Li, Xiang Wei, Wei Dai, Xuan Yang, Bangkun Liu, Wen Shu, Bing Wang, Mengyang Lu, Taojunjin Cai, Yuankun Zheng, Zhixin Mei, Zhimin Zhou, Yixuan Yang, Jingyi Zhao, Jingwei Shen, Lei Ho, Joshua Wing Kei Chen, Jincao Xiong, Nanxiang |
author_facet | Cai, Meng Chai, Songshan Xiong, Tao Wei, Jun Mao, Weibing Zhu, Yasha Li, Xiang Wei, Wei Dai, Xuan Yang, Bangkun Liu, Wen Shu, Bing Wang, Mengyang Lu, Taojunjin Cai, Yuankun Zheng, Zhixin Mei, Zhimin Zhou, Yixuan Yang, Jingyi Zhao, Jingwei Shen, Lei Ho, Joshua Wing Kei Chen, Jincao Xiong, Nanxiang |
author_sort | Cai, Meng |
collection | PubMed |
description | A group of circulating microRNAs (miRNAs) have been implicated in the pathogenesis of Parkinson’s disease. However, a comprehensive study of the interactions between pathogenic miRNAs and their downstream Parkinson’s disease (PD)-related target genes has not been performed. Here, we identified the miRNA expression profiles in the plasma and circulating exosomes of Parkinson’s disease patients using next-generation RNA sequencing. Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) analyses showed that the miRNA target genes were enriched in axon guidance, neurotrophin signaling, cellular senescence, and the Transforming growth factor-β (TGF-β), mitogen-activated protein kinase (MAPK), phosphatidylinositol 3-kinase (PI3K)-protein kinase B (AKT) and mechanistic target of rapamycin (mTOR) signaling pathways. Furthermore, a group of aberrantly expressed miRNAs were selected and further validated in individual patient plasma, human neural stem cells (NSCs) and a rat model of PD. More importantly, the full scope of the regulatory network between these miRNAs and their PD-related gene targets in human neural stem cells was examined, and the findings revealed a similar but still varied downstream regulatory cascade involving many known PD-associated genes. Additionally, miR-23b-3p was identified as a novel direct regulator of alpha-synuclein, which is possibly the key component in PD. Our current study, for the first time, provides a glimpse into the regulatory network of pathogenic miRNAs and their PD-related gene targets in PD. Moreover, these PD-associated miRNAs may serve as biomarkers and novel therapeutic targets for PD. |
format | Online Article Text |
id | pubmed-8419519 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-84195192021-09-07 Aberrant Expression of Circulating MicroRNA Leads to the Dysregulation of Alpha-Synuclein and Other Pathogenic Genes in Parkinson’s Disease Cai, Meng Chai, Songshan Xiong, Tao Wei, Jun Mao, Weibing Zhu, Yasha Li, Xiang Wei, Wei Dai, Xuan Yang, Bangkun Liu, Wen Shu, Bing Wang, Mengyang Lu, Taojunjin Cai, Yuankun Zheng, Zhixin Mei, Zhimin Zhou, Yixuan Yang, Jingyi Zhao, Jingwei Shen, Lei Ho, Joshua Wing Kei Chen, Jincao Xiong, Nanxiang Front Cell Dev Biol Cell and Developmental Biology A group of circulating microRNAs (miRNAs) have been implicated in the pathogenesis of Parkinson’s disease. However, a comprehensive study of the interactions between pathogenic miRNAs and their downstream Parkinson’s disease (PD)-related target genes has not been performed. Here, we identified the miRNA expression profiles in the plasma and circulating exosomes of Parkinson’s disease patients using next-generation RNA sequencing. Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) analyses showed that the miRNA target genes were enriched in axon guidance, neurotrophin signaling, cellular senescence, and the Transforming growth factor-β (TGF-β), mitogen-activated protein kinase (MAPK), phosphatidylinositol 3-kinase (PI3K)-protein kinase B (AKT) and mechanistic target of rapamycin (mTOR) signaling pathways. Furthermore, a group of aberrantly expressed miRNAs were selected and further validated in individual patient plasma, human neural stem cells (NSCs) and a rat model of PD. More importantly, the full scope of the regulatory network between these miRNAs and their PD-related gene targets in human neural stem cells was examined, and the findings revealed a similar but still varied downstream regulatory cascade involving many known PD-associated genes. Additionally, miR-23b-3p was identified as a novel direct regulator of alpha-synuclein, which is possibly the key component in PD. Our current study, for the first time, provides a glimpse into the regulatory network of pathogenic miRNAs and their PD-related gene targets in PD. Moreover, these PD-associated miRNAs may serve as biomarkers and novel therapeutic targets for PD. Frontiers Media S.A. 2021-08-23 /pmc/articles/PMC8419519/ /pubmed/34497805 http://dx.doi.org/10.3389/fcell.2021.695007 Text en Copyright © 2021 Cai, Chai, Xiong, Wei, Mao, Zhu, Li, Wei, Dai, Yang, Liu, Shu, Wang, Lu, Cai, Zheng, Mei, Zhou, Yang, Zhao, Shen, Ho, Chen and Xiong. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Cell and Developmental Biology Cai, Meng Chai, Songshan Xiong, Tao Wei, Jun Mao, Weibing Zhu, Yasha Li, Xiang Wei, Wei Dai, Xuan Yang, Bangkun Liu, Wen Shu, Bing Wang, Mengyang Lu, Taojunjin Cai, Yuankun Zheng, Zhixin Mei, Zhimin Zhou, Yixuan Yang, Jingyi Zhao, Jingwei Shen, Lei Ho, Joshua Wing Kei Chen, Jincao Xiong, Nanxiang Aberrant Expression of Circulating MicroRNA Leads to the Dysregulation of Alpha-Synuclein and Other Pathogenic Genes in Parkinson’s Disease |
title | Aberrant Expression of Circulating MicroRNA Leads to the Dysregulation of Alpha-Synuclein and Other Pathogenic Genes in Parkinson’s Disease |
title_full | Aberrant Expression of Circulating MicroRNA Leads to the Dysregulation of Alpha-Synuclein and Other Pathogenic Genes in Parkinson’s Disease |
title_fullStr | Aberrant Expression of Circulating MicroRNA Leads to the Dysregulation of Alpha-Synuclein and Other Pathogenic Genes in Parkinson’s Disease |
title_full_unstemmed | Aberrant Expression of Circulating MicroRNA Leads to the Dysregulation of Alpha-Synuclein and Other Pathogenic Genes in Parkinson’s Disease |
title_short | Aberrant Expression of Circulating MicroRNA Leads to the Dysregulation of Alpha-Synuclein and Other Pathogenic Genes in Parkinson’s Disease |
title_sort | aberrant expression of circulating microrna leads to the dysregulation of alpha-synuclein and other pathogenic genes in parkinson’s disease |
topic | Cell and Developmental Biology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8419519/ https://www.ncbi.nlm.nih.gov/pubmed/34497805 http://dx.doi.org/10.3389/fcell.2021.695007 |
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