Dataset Information

Genome?wide DNA methylation profiling in a rat model with vascular dementia.

ABSTRACT: Vascular dementia (VaD), the second most prevalent type of dementia, is caused by reduced blood supply to the brain that results in cognitive impairment. Despite the efforts of numerous studies, the pathological mechanisms behind VaD remain unclear. The aim of the present study was to identify candidate genes that undergo changes in hippocampal DNA methylation owing to VaD. A genome?wide DNA methylation analysis was performed, using methylated DNA?binding domain sequencing. VaD model rats with cognitive impairment induced by bilateral common carotid artery occlusion were confirmed using the radial arm maze test. A total of 1,180 differentially methylated genes (DMGs) were identified, and functional annotation analysis revealed the DMGs to be enriched in 10 Gene Ontology biological processes. Network analysis using the STRING database indicated that seven genes were closely connected. Rats in the VaD model group demonstrated relative hypomethylation in the promoter region and increased mRNA expression of the hippocampal genes vascular endothelial growth factor (VEGFA) and kinase insert domain receptor, but only differences in VEGFA mRNA expression levels were determined to be statistically significant. In conclusion, these preliminary data from the functional annotation of hippocampal DMGs in the promoter region highlighted candidate genes for VaD that may contribute to the elucidation of its pathophysiology.

SUBMITTER: Park JM

PROVIDER: S-EPMC6059660 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature

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Genome‑wide DNA methylation profiling in a rat model with vascular dementia.

Park Jong-Min JM Kim Yoon Ju YJ Song Min Kyung MK Lee Jae-Min JM Kim Youn-Jung YJ

Molecular medicine reports 20180508 1

Vascular dementia (VaD), the second most prevalent type of dementia, is caused by reduced blood supply to the brain that results in cognitive impairment. Despite the efforts of numerous studies, the pathological mechanisms behind VaD remain unclear. The aim of the present study was to identify candidate genes that undergo changes in hippocampal DNA methylation owing to VaD. A genome‑wide DNA methylation analysis was performed, using methylated DNA‑binding domain sequencing. VaD model rats with c ...[more]

PMID: 29749552

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Project description:Chordomas are an aggressive rare type of malignant bone tumors arising from the remnant of the notochord. Chordomas occur mainly in vertebral bones and account for 1-4% of malignant bone tumors. Management and treatment of chordomas are difficult as they are resistant to conventional chemotherapy; therefore, they are mainly treated with surgery and radiation therapy. In this study, we performed DNA methylation profiling of 26 chordomas and normal nucleus pulposus samples plus UCH-1 chordoma cell line using the Illumina Infinium HumanMethylation450 BeadChips. Combined bisulfite restriction analysis and bisulfite sequencing was used to confirm the methylation data. Gene expression was analyzed using RT-PCR before and after 5-aza-2'-deoxycytidine (5-azaDC) treatment of chordoma cell lines. Analysis of the HumanMethylation450 BeadChip data led to the identification of 8,819 loci (2.9%) that were significantly differentially methylated (>0.2 average ?-value difference) between chordomas and nucleus pulposus samples (adjusted P < 0.05). Among these, 5,868 probes (66.5%) were hypomethylated, compared to 2,951 (33.5%) loci that were hypermethylated in chordomas compared to controls. From the 2,951 differentially hypermethylated probes, 33.3% were localized in the promoter region (982 probes) and, among these, 104 probes showed cancer-specific hypermethylation. Ingenuity Pathway Analysis indicates that the cancer-specific differentially methylated loci are involved in various networks including cancer disease, nervous system development and function, cell death and survival, cellular growth, cellular development, and proliferation. Furthermore, we identified a subset of probes that were differentially methylated between recurrent and non-recurrent chordomas. BeadChip methylation data was confirmed for these genes and gene expression was shown to be upregulated in methylated chordoma cell lines after treatment with 5-azaDC. Understanding epigenetic changes in chordomas may provide insights into chordoma tumorigenesis and development of epigenetic biomarkers.

Dataset Information

Genome?wide DNA methylation profiling in a rat model with vascular dementia.

Publications

Genome‑wide DNA methylation profiling in a rat model with vascular dementia.

Similar Datasets

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