Dataset Information

The Potential Regulatory Mechanisms of miR-196a in Huntington's Disease through Bioinformatic Analyses.

ABSTRACT: High throughput screening is a powerful tool to identify the potential candidate molecules involved during disease progression. However, analysis of complicated data is one of the most challenging steps on the way to obtaining useful results from this approach. Previously, we showed that a specific miRNA, miR-196a, could ameliorate the pathological phenotypes of Huntington's disease (HD) in different models, and performed high throughput screening by using the striatum of transgenic mice. In this study, we further tried to identify the potential regulatory mechanisms using different bioinformatic tools, including Database for Annotation, Visualization and Integrated Discovery (DAVID), Molecular Signatures Database (MSigDB), TargetScan and MetaCore. The results showed that miR-196a dominantly altered "ABC transporters", "RIG-I-like receptor signaling pathway", immune system", "adaptive immune system","tissue remodeling and wound repair" and "cytoskeleton remodeling". In addition, miR-196a also changed the expression of several well-defined pathways of HD, such as apoptosis and cell adhesion. Since these analyses showed the regulatory pathways are highly related to the modification of the cytoskeleton, we further confirmed that miR-196a could enhance the neurite outgrowth in neuroblastoma cells, suggesting miR-196a might provide beneficial functions through the alteration of cytoskeleton structures. Since impairment of the cytoskeleton has been reported in several neuronal diseases, this study will provide not only the potential working mechanisms of miR-196a but also insights for therapeutic strategies for use with different neuronal diseases.

SUBMITTER: Fu MH

PROVIDER: S-EPMC4574104 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

The Potential Regulatory Mechanisms of miR-196a in Huntington's Disease through Bioinformatic Analyses.

Fu Mu-Hui MH Li Chia-Ling CL Lin Hsiu-Lien HL Tsai Shaw-Jeng SJ Lai Yen-Yu YY Chang Yu-Fan YF Cheng Pei-Hsun PH Chen Chuan-Mu CM Yang Shang-Hsun SH

PloS one 20150916 9

High throughput screening is a powerful tool to identify the potential candidate molecules involved during disease progression. However, analysis of complicated data is one of the most challenging steps on the way to obtaining useful results from this approach. Previously, we showed that a specific miRNA, miR-196a, could ameliorate the pathological phenotypes of Huntington's disease (HD) in different models, and performed high throughput screening by using the striatum of transgenic mice. In thi ...[more]

PMID: 26376480

Similar Datasets

Project description:BackgroundHuntington's disease (HD) is a neurodegenerative disorder characterized by psychiatric symptoms, serious motor and cognitive deficits. Certain pathological changes can already be observed in pre-symptomatic HD (pre-HD) patients; however, the underlying molecular pathogenesis is still uncertain and no effective treatments are available until now. Here, we reanalyzed HD-related differentially expressed genes from the GEO database between symptomatic HD patients, pre-HD individuals, and healthy controls using bioinformatics analysis, hoping to get more insight in the pathogenesis of both pre-HD and HD, and shed a light in the potential therapeutic targets of the disease.MethodsPre-HD and symptomatic HD differentially expressed genes (DEGs) were screened by bioinformatics analysis Gene Expression Omnibus (GEO) dataset GSE1751. A protein-protein interaction (PPI) network was used to select hub genes. Subsequently, Gene Ontology (GO) enrichment analysis of DEGs and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis of hub genes were applied. Dataset GSE24250 was downloaded to verify our hub genes by the Kaplan-Meier method using Graphpad Prism 5.0. Finally, target miRNAs of intersected hub genes involved in pre-HD and symptomatic HD were predicted.ResultsA total of 37 and 985 DEGs were identified in pre-HD and symptomatic HD, respectively. The hub genes, SIRT1, SUZ12, and PSMC6, may be implicated in pre-HD, and the hub genes, FIS1, SIRT1, CCNH, SUZ12, and 10 others, may be implicated in symptomatic HD. The intersected hub genes, SIRT1 and SUZ12, and their predicted target miRNAs, in particular miR-22-3p and miR-19b, may be significantly associated with pre-HD.ConclusionThe PSMC6, SIRT1, and SUZ12 genes and their related ubiquitin-mediated proteolysis, transcriptional dysregulation, and histone metabolism are significantly associated with pre-HD. FIS1, CCNH, and their related mitochondrial disruption and transcriptional dysregulation processes are related to symptomatic HD, which might shed a light on the elucidation of potential therapeutic targets in HD.

Dataset Information

The Potential Regulatory Mechanisms of miR-196a in Huntington's Disease through Bioinformatic Analyses.

Publications

The Potential Regulatory Mechanisms of miR-196a in Huntington's Disease through Bioinformatic Analyses.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets