Transcriptomics,Multiomics

Dataset Information

5

Identification of novel markers in rheumatoid arthritis through integrated analysis of DNA methylation and microRNA expression


ABSTRACT: Autoimmune rheumatic diseases are complex disorders, whose etiopathology is attributed to a crosstalk between genetic predisposition and environmental factors. Both variants of autoimmune susceptibility genes and environment are involved in the generation of aberrant epigenetic profiles in a cell-specific manner, which ultimately result in dysregulation of expression. Furthermore, changes in miRNA expression profiles also cause gene dysregulation associated with aberrant phenotypes. In rheumatoid arthritis, several cell types are involved in the destruction of the joints, synovial fibroblasts being among the most important. In this study we performed DNA methylation and miRNA expression screening of a set of rheumatoid arthritis synovial fibroblasts and compared the results with those obtained from osteoarthritis patients with a normal phenotype. DNA methylation screening allowed us to identify changes in novel key target genes like IL6R, CAPN8 and DPP4, as well as several HOX genes. A significant proportion of genes undergoing DNA methylation changes were inversely correlated with expression. miRNA screening revealed the existence of subsets of miRNAs that underwent changes in expression. Integrated analysis highlighted sets of miRNAs that are controlled by DNA methylation, and genes that are regulated by DNA methylation and are targeted by miRNAs with a potential use as clinical markers. Our study enabled the identification of novel dysregulated targets in rheumatoid arthritis synovial fibroblasts and generated a new workflow for the integrated analysis of miRNA and epigenetic control. Comparison between the DNA methylation levels of synovial fibroblasts isolated from 6 Osteoarthritis and 6 Rheumatoid arthritis patients isolated from synovial tissues at the time of joint replacement. Bisulphite converted DNA from the 12 samples were hybridised to the Illumina Infinium 450k Human Methylation Beadchip

OTHER RELATED OMICS DATASETS IN: PRJNA201405

SUBMITTER: René E Toes   José M Urquiza  Abul B Islam  Esteban Ballestar  Lorenzo de la Rica  David Gómez-Cabrero  Jesper Tegnér  Nuria López-Bigas 

PROVIDER: E-GEOD-46650 | ArrayExpress | 2013-05-07

SECONDARY ACCESSION(S): GSE46650PRJNA201405

REPOSITORIES: GEO, ArrayExpress

Dataset's files

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Action DRS
E-GEOD-46650.additional.1.zip Other
E-GEOD-46650.idf.txt Idf
E-GEOD-46650.processed.1.zip Processed
E-GEOD-46650.sdrf.txt Txt
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Publications

Identification of novel markers in rheumatoid arthritis through integrated analysis of DNA methylation and microRNA expression.

de la Rica Lorenzo L   Urquiza José M JM   Gómez-Cabrero David D   Islam Abul B M M K AB   López-Bigas Nuria N   Tegnér Jesper J   Toes René E M RE   Ballestar Esteban E  

Journal of autoimmunity 20130108


Autoimmune rheumatic diseases are complex disorders, whose etiopathology is attributed to a crosstalk between genetic predisposition and environmental factors. Both variants of autoimmune susceptibility genes and environment are involved in the generation of aberrant epigenetic profiles in a cell-specific manner, which ultimately result in dysregulation of expression. Furthermore, changes in miRNA expression profiles also cause gene dysregulation associated with aberrant phenotypes. In rheumatoi  ...[more]

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