Non-coding RNA network associated with obesity and rheumatoid arthritis

Abstract

Obesity causes epigenetic alterations mediated by non-coding RNAs (ncRNAs) that increase susceptibility to autoimmune and inflammatory pathways. Obese individuals with rheumatoid arthritis (RA) are particularly affected, with worse clinical outcomes and treatment responses. In order to identify micro RNAs (miRNAs) and long ncRNAs (lncRNAs) that may influence RA development, progression, treatment efficacy, and clinical outcomes in obese individuals, we systematically screened PubMed, Web of Science, and Scopus databases for articles on these topics, published in the last decade. We ended up with 38 of initially 1110 documents and found that both obesity and RA share dysregulated expression of miR-21, miR-143, miR-146a, miR-155 miRNAs, H19, and HOTAIR lncRNAs (all but H19, up-regulated). With one exception (H19 and BMI in brown fat tissue), they correlated positively with clinical measures and disease activity. H19 and HOTAIR regulate 24 miRNAs, some differentially expressed in the investigated diseases. Both regulate miR-143-3p. We also investigated eleven GWAS-identified SNVs found in exonic lncRNA regions (there were none in exonic miRNA genes). Eight were associated with RA and three with obesity-related traits, seven change binding sites for miRNAs, especially on LINC01184 and GATA3-AS1, four were associated with gene expression in adipocytes (including LINC01184) and two may also change the secondary structure of ENSG00000284825 and LINC02656. These ncRNAs compose a unique regulatory network in obese RA patients, compiled for the first time in this review, which we suggest as future therapeutic targets in these simultaneous conditions.

Keywords: Autoimmune; Obesity; Rheumatoid arthritis; lncRNA; miRNA; ncRNA.