Identification of Potential miRNA-mRNA Regulatory Network Contributing to Parkinson’s Disease
Parkinson’s disease (PD) is a common neurodegenerative disease, and the mechanism underlying PD pathogenesis is not completely understood. Increasing evidence indicates that microRNAs (miRNAs) play a critical regulatory role in the pathogenesis of PD. This study aimed to explore the miRNA-mRNA regul...
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| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2022-01-01
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| Series: | Parkinson's Disease |
| Online Access: | http://dx.doi.org/10.1155/2022/2877728 |
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| _version_ | 1832562363794980864 |
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| author | Xi Yin Miao Wang Wei Wang Tong Chen Ge Song Yixuan Niu Ziying Jiang Zhongbao Gao Zhenfu Wang |
| author_facet | Xi Yin Miao Wang Wei Wang Tong Chen Ge Song Yixuan Niu Ziying Jiang Zhongbao Gao Zhenfu Wang |
| author_sort | Xi Yin |
| collection | DOAJ |
| description | Parkinson’s disease (PD) is a common neurodegenerative disease, and the mechanism underlying PD pathogenesis is not completely understood. Increasing evidence indicates that microRNAs (miRNAs) play a critical regulatory role in the pathogenesis of PD. This study aimed to explore the miRNA-mRNA regulatory network for PD. The differentially expressed miRNAs (DEmis) and genes (DEGs) between PD patients and healthy donors were screened from the miRNA dataset GSE16658 and mRNA dataset GSE100054 downloaded from the Gene Expression Omnibus (GEO) database. Target genes of the DEmis were selected when they were predicted by three or four online databases and overlapped with DEGs from GSE100054. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were then conducted by Database for Annotation, Visualization and Integrated Discovery (DAVID) and Metascape analytic tools. The correlation between the screened genes and PD was evaluated with the online tool Comparative Toxicogenomics Database (CTD), and protein-protein interaction (PPI) networks were built by the STRING platform. We further investigated the expression of genes in the miRNA-mRNA regulatory network in blood samples collected from PD patients and healthy donors via qRT-PCR. We identified 1505 upregulated and 1302 downregulated DEGs, and 77 upregulated and 112 downregulated DEmis were preliminarily screened from the GEO database. Further functional enrichment analysis identified 10 PD-related hub genes, including RAC1, IRS2, LEPR, PPARGC1A, CAMKK2, RAB10, RAB13, RAB27B, RAB11A, and JAK2, which were mainly involved in Rab protein signaling transduction, AMPK signaling pathway, and signaling by Leptin. A miRNA-mRNA regulatory network was then constructed with 10 hub genes, and their interacting miRNAs overlapped with DEmis, including miR-30e-5p, miR-142-3p, miR-101-3p, miR-32-3p, miR-508-5p, miR-642a-5p, miR-19a-3p, and miR-21-5p. Analysis of clinical samples verified significant upregulation of LEPR and downregulation of miR-101-3p and miR-30e-5p in PD patients as compared with healthy donors. Thus, the miRNA-mRNA regulatory network was initially constructed and has the potential to provide novel insights into the pathogenesis and treatment of PD. |
| format | Article |
| id | doaj-art-bf8c725eda184e8ba6fa669da5709703 |
| institution | Kabale University |
| issn | 2042-0080 |
| language | English |
| publishDate | 2022-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Parkinson's Disease |
| spelling | doaj-art-bf8c725eda184e8ba6fa669da57097032025-02-03T01:22:49ZengWileyParkinson's Disease2042-00802022-01-01202210.1155/2022/2877728Identification of Potential miRNA-mRNA Regulatory Network Contributing to Parkinson’s DiseaseXi Yin0Miao Wang1Wei Wang2Tong Chen3Ge Song4Yixuan Niu5Ziying Jiang6Zhongbao Gao7Zhenfu Wang8Department of NeurologyDepartment of NeurologyDepartment of NeurologyDepartment of NeurologyDepartment of GeriatricsDepartment of GeriatricsDepartment of NeurologyDepartment of NeurologyDepartment of NeurologyParkinson’s disease (PD) is a common neurodegenerative disease, and the mechanism underlying PD pathogenesis is not completely understood. Increasing evidence indicates that microRNAs (miRNAs) play a critical regulatory role in the pathogenesis of PD. This study aimed to explore the miRNA-mRNA regulatory network for PD. The differentially expressed miRNAs (DEmis) and genes (DEGs) between PD patients and healthy donors were screened from the miRNA dataset GSE16658 and mRNA dataset GSE100054 downloaded from the Gene Expression Omnibus (GEO) database. Target genes of the DEmis were selected when they were predicted by three or four online databases and overlapped with DEGs from GSE100054. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were then conducted by Database for Annotation, Visualization and Integrated Discovery (DAVID) and Metascape analytic tools. The correlation between the screened genes and PD was evaluated with the online tool Comparative Toxicogenomics Database (CTD), and protein-protein interaction (PPI) networks were built by the STRING platform. We further investigated the expression of genes in the miRNA-mRNA regulatory network in blood samples collected from PD patients and healthy donors via qRT-PCR. We identified 1505 upregulated and 1302 downregulated DEGs, and 77 upregulated and 112 downregulated DEmis were preliminarily screened from the GEO database. Further functional enrichment analysis identified 10 PD-related hub genes, including RAC1, IRS2, LEPR, PPARGC1A, CAMKK2, RAB10, RAB13, RAB27B, RAB11A, and JAK2, which were mainly involved in Rab protein signaling transduction, AMPK signaling pathway, and signaling by Leptin. A miRNA-mRNA regulatory network was then constructed with 10 hub genes, and their interacting miRNAs overlapped with DEmis, including miR-30e-5p, miR-142-3p, miR-101-3p, miR-32-3p, miR-508-5p, miR-642a-5p, miR-19a-3p, and miR-21-5p. Analysis of clinical samples verified significant upregulation of LEPR and downregulation of miR-101-3p and miR-30e-5p in PD patients as compared with healthy donors. Thus, the miRNA-mRNA regulatory network was initially constructed and has the potential to provide novel insights into the pathogenesis and treatment of PD.http://dx.doi.org/10.1155/2022/2877728 |
| spellingShingle | Xi Yin Miao Wang Wei Wang Tong Chen Ge Song Yixuan Niu Ziying Jiang Zhongbao Gao Zhenfu Wang Identification of Potential miRNA-mRNA Regulatory Network Contributing to Parkinson’s Disease Parkinson's Disease |
| title | Identification of Potential miRNA-mRNA Regulatory Network Contributing to Parkinson’s Disease |
| title_full | Identification of Potential miRNA-mRNA Regulatory Network Contributing to Parkinson’s Disease |
| title_fullStr | Identification of Potential miRNA-mRNA Regulatory Network Contributing to Parkinson’s Disease |
| title_full_unstemmed | Identification of Potential miRNA-mRNA Regulatory Network Contributing to Parkinson’s Disease |
| title_short | Identification of Potential miRNA-mRNA Regulatory Network Contributing to Parkinson’s Disease |
| title_sort | identification of potential mirna mrna regulatory network contributing to parkinson s disease |
| url | http://dx.doi.org/10.1155/2022/2877728 |
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