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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...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
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.
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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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