4.5 Article

Identification of Biomolecular Information in Rotenone-Induced Cellular Model of Parkinson's Disease by Public Microarray Data Analysis

Journal

JOURNAL OF COMPUTATIONAL BIOLOGY
Volume 27, Issue 6, Pages 888-903

Publisher

MARY ANN LIEBERT, INC
DOI: 10.1089/cmb.2019.0151

Keywords

Gene Ontology; miRNA-target; Parkinson's disease; pathway; protein-protein interaction; rotenone

Funding

  1. Shanghai Science and Technology Committee and Scientific Research and Innovation Team Funding Plan of Shanghai Sanda University [16411955200]
  2. Shanghai Rehabilitation Research Project for the Disabled [K2016018]

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To explore the expression changes of genes and the pathological processes-related genetic information in Parkinson's disease (PD) model induced by rotenone. The microarray data set GSE37178 was downloaded from Gene Expression Omnibus database. Differentially expression genes (DEGs) at different concentration and time points were examined and clustered using Mfuzz. Functional enrichment was analyzed with The Database for Annotation, Visualization and Integrated Discovery. Search Tool for the Retrieval of Interacting Genes was used to perform the protein-protein interaction (PPI) networks, and functional module analysis of PPI was constructed with Cytoscape. Moreover, transcription factors (TFs) and microRNA (miRNA) target were screened with TRRUST and WebGestalt GAST, respectively. In total, 680 DEGs were examined in the group with rotenone treatment. Clustering analysis revealed that 115 genes presented a consistent rising trend, and 138 genes presented a falling trend. Functional enrichment analysis uncovered that the upregulated genes associated with type I interferon signaling pathway, and the downregulated genes were related to proteasome-mediated ubiquitin-dependent protein catabolic process. The PPI network included 156 nodes and 298 interactions, and ISG15, RRM2, FBXW11, and FOXM1 were the hub genes. Meanwhile, 38 TF-target and 269 miRNA-target interactions were obtained; the mRNAs of the MIR-181 family have more target genes, such as TRIM13. Our study showed that aberrant expression of ISG15, RRM2, FBXW11, FOXM1, and MIR-181 family were associated with pathological processes in PD, and they could be the research focuses to further investigate the mechanism of PD.

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