Dataset Information

Integrated Genome-Wide Methylation and Expression Analyses Reveal Key Regulators in Osteosarcoma.

ABSTRACT: Osteosarcoma (OS) is one of the most common types of primary bone tumors in early adolescence with unsatisfied prognosis. Aberrant DNA methylation had been demonstrated to be related to tumorigenesis and progression of multiple cancers and could serve as the potential biomarkers for the prognosis of human cancers. In conclusion, this study identified 18 downregulated hypomethylation genes and 52 upregulated hypomethylation genes in OS by integrating the analysis the GSE97529 and GSE42572 datasets. Bioinformatics analysis revealed that OS-specific methylated genes were involved in regulating multiple biological processes, including chemical synaptic transmission, transcription, response to drug, and regulating immune response. KEGG pathway analysis showed that OS-specific methylated genes were associated with the regulation of Hippo, cAMP calcium, MAPK, and Wnt signaling pathways. By analyzing R2 datasets, this study showed that the dysregulation of these OS-specific methylated genes was associated with the metastasis-free survival time in patients with OS, including CBLN4, ANKMY1, BZW1, KRTCAP3, GZMB, KRTDAP, LY9, PFKFB2, PTPN22, and CLDN7. This study provided a better understanding of the molecular mechanisms underlying the progression and OS and novel biomarkers for the prognosis of OS.

SUBMITTER: Wang F

PROVIDER: S-EPMC7443031 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Integrated Genome-Wide Methylation and Expression Analyses Reveal Key Regulators in Osteosarcoma.

Wang Fei F Qin Guoqing G Liu Junzhi J Wang Xiunan X Ye Baoguo B

Computational and mathematical methods in medicine 20200813

Osteosarcoma (OS) is one of the most common types of primary bone tumors in early adolescence with unsatisfied prognosis. Aberrant DNA methylation had been demonstrated to be related to tumorigenesis and progression of multiple cancers and could serve as the potential biomarkers for the prognosis of human cancers. In conclusion, this study identified 18 downregulated hypomethylation genes and 52 upregulated hypomethylation genes in OS by integrating the analysis the GSE97529 and GSE42572 dataset ...[more]

PMID: 32855654

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Project description:BackgroundWool fibers are valuable materials for textile industry. Typical wool fibers are divided into medullated and non-medullated types, with the former generated from primary wool follicles and the latter by either primary or secondary wool follicles. The medullated wool is a common wool type in the ancestors of fine wool sheep before breeding. The fine wool sheep have a non-medullated coat. However, the critical period determining the type of wool follicles is the embryonic stage, which limits the phenotypic observation and variant contrast, making both selection and studies of wool type variation fairly difficult.ResultsDuring the breeding of a modern fine (MF) wool sheep population with multiple-ovulation and embryo transfer technique, we serendipitously discovered lambs with ancestral-like coarse (ALC) wool. Whole-genome resequencing confirmed ALC wool lambs as a variant type from the MF wool population. We mapped the significantly associated methylation locus on chromosome 4 by using whole genome bisulfite sequencing signals, and in turn identified the SOSTDC1 gene as exons hypermethylated in ALC wool lambs compare to their half/full sibling MF wool lambs. Transcriptome sequencing found that SOSTDC1 was expressed dozens of times more in ALC wool lamb skin than that of MF and was at the top of all differentially expressed genes. An analogy with the transcriptome of coarse/fine wool breeds revealed that differentially expressed genes and enriched pathways at postnatal lamb stage in ALC/MF were highly similar to those at the embryonic stage in the former. Further experiments validated that the SOSTDC1 gene was specifically highly expressed in the nucleus of the dermal papilla of primary wool follicles.ConclusionIn this study, we conducted genome-wide differential methylation site association analysis on differential wool type trait, and located the only CpG locus that strongly associated with primary wool follicle development. Combined with transcriptome analysis, SOSTDC1 was identified as the only gene at this locus that was specifically overexpressed in the primary wool follicle stem cells of ALC wool lamb skin. The discovery of this key gene and its epigenetic regulation contributes to understanding the domestication and breeding of fine wool sheep.

Project description:Background:Alu elements are a group of repetitive elements that can influence gene expression through CpG residues and transcription factor binding. Altered gene expression and methylation profiles have been reported in various tissues and cell lines from individuals with autism spectrum disorder (ASD). However, the role of Alu elements in ASD remains unclear. We thus investigated whether Alu elements are associated with altered gene expression profiles in ASD. Methods:We obtained five blood-based gene expression profiles from the Gene Expression Omnibus database and human Alu-inserted gene lists from the TranspoGene database. Differentially expressed genes (DEGs) in ASD were identified from each study and overlapped with the human Alu-inserted genes. The biological functions and networks of Alu-inserted DEGs were then predicted by Ingenuity Pathway Analysis (IPA). A combined bisulfite restriction analysis of lymphoblastoid cell lines (LCLs) derived from 36 ASD and 20 sex- and age-matched unaffected individuals was performed to assess the global DNA methylation levels within Alu elements, and the Alu expression levels were determined by quantitative RT-PCR. Results:In ASD blood or blood-derived cells, 320 Alu-inserted genes were reproducibly differentially expressed. Biological function and pathway analysis showed that these genes were significantly associated with neurodevelopmental disorders and neurological functions involved in ASD etiology. Interestingly, estrogen receptor and androgen signaling pathways implicated in the sex bias of ASD, as well as IL-6 signaling and neuroinflammation signaling pathways, were also highlighted. Alu methylation was not significantly different between the ASD and sex- and age-matched control groups. However, significantly altered Alu methylation patterns were observed in ASD cases sub-grouped based on Autism Diagnostic Interview-Revised scores compared with matched controls. Quantitative RT-PCR analysis of Alu expression also showed significant differences between ASD subgroups. Interestingly, Alu expression was correlated with methylation status in one phenotypic ASD subgroup. Conclusion:Alu methylation and expression were altered in LCLs from ASD subgroups. Our findings highlight the association of Alu elements with gene dysregulation in ASD blood samples and warrant further investigation. Moreover, the classification of ASD individuals into subgroups based on phenotypes may be beneficial and could provide insights into the still unknown etiology and the underlying mechanisms of ASD.

Project description:BackgroundSmoking is a major causal risk factor for lung cancer, chronic obstructive pulmonary disease (COPD), cardiovascular disease (CVD), and is the main preventable cause of deaths in the world. The components of cigarette smoke are involved in immune and inflammatory processes, which may increase the prevalence of cigarette smoke-related diseases. However, the underlying molecular mechanisms linking smoking and diseases have not been well explored. This study was aimed to depict a global map of DNA methylation and gene expression changes induced by tobacco smoking and to explore the molecular mechanisms between smoking and human diseases through whole-genome bisulfite sequencing (WGBS) and RNA-sequencing (RNA-seq).ResultsWe performed WGBS on 72 samples (36 smokers and 36 nonsmokers) and RNA-seq on 75 samples (38 smokers and 37 nonsmokers), and cytokine immunoassay on plasma from 22 males (9 smokers and 13 nonsmokers) who were recruited from the city of Jincheng in China. By comparing the data of the two groups, we discovered a genome-wide methylation landscape of differentially methylated regions (DMRs) associated with smoking. Functional enrichment analyses revealed that both smoking-related hyper-DMR genes (DMGs) and hypo-DMGs were related to synapse-related pathways, whereas the hypo-DMGs were specifically related to cancer and addiction. The differentially expressed genes (DEGs) revealed by RNA-seq analysis were significantly enriched in the "immunosuppression" pathway. Correlation analysis of DMRs with their corresponding gene expression showed that genes affected by tobacco smoking were mostly related to immune system diseases. Finally, by comparing cytokine concentrations between smokers and nonsmokers, we found that vascular endothelial growth factor (VEGF) was significantly upregulated in smokers.ConclusionsIn sum, we found that smoking-induced DMRs have different distribution patterns in hypermethylated and hypomethylated areas between smokers and nonsmokers. We further identified and verified smoking-related DMGs and DEGs through multi-omics integration analysis of DNA methylome and transcriptome data. These findings provide us a comprehensive genomic map of the molecular changes induced by smoking which would enhance our understanding of the harms of smoking and its relationship with diseases.

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Dataset Information

Integrated Genome-Wide Methylation and Expression Analyses Reveal Key Regulators in Osteosarcoma.

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Integrated Genome-Wide Methylation and Expression Analyses Reveal Key Regulators in Osteosarcoma.

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