TY - JOUR
T1 - Identification of novel markers in rheumatoid arthritis through integrated analysis of DNA methylation and microRNA expression
AU - de la Rica, Lorenzo
AU - Urquiza, José M.
AU - Gómez-Cabrero, David
AU - Islam, Abul B.M.M.K.
AU - López-Bigas, Nuria
AU - Tegnér, Jesper
AU - Toes, René E.M.
AU - Ballestar, Esteban
N1 - Generated from Scopus record by KAUST IRTS on 2021-02-16
PY - 2013/3/1
Y1 - 2013/3/1
N2 - 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. © 2012 Elsevier Ltd.
AB - 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. © 2012 Elsevier Ltd.
UR - https://linkinghub.elsevier.com/retrieve/pii/S0896841112001515
UR - http://www.scopus.com/inward/record.url?scp=84875943253&partnerID=8YFLogxK
U2 - 10.1016/j.jaut.2012.12.005
DO - 10.1016/j.jaut.2012.12.005
M3 - Article
C2 - 23306098
SN - 0896-8411
VL - 41
SP - 6
EP - 16
JO - Journal of Autoimmunity
JF - Journal of Autoimmunity
ER -