Abstract
Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease driven by genetic, environmental and epigenetic factors. Long non-coding RNAs (LncRNAs) are a key component of the epigenetic mechanisms and are known to be involved in the development of autoimmune diseases. In this work we aimed to identify significantly differentially expressed LncRNAs (DE-LncRNAs) that are functionally connected to modulated genes strictly associated with RA. In total, 542,500 transcripts have been profiled in peripheral blood mononuclear cells (PBMCs) from four patients with early onset RA prior any treatment and four healthy donors using Clariom D arrays. Results were confirmed by real-time PCR in 20 patients and 20 controls. Six DE-LncRNAs target experimentally validated miRNAs able to regulate differentially expressed genes (DEGs) in RA; among them, only FTX, HNRNPU-AS1 and RP11-498C9.15 targeted a large number of DEGs. Most importantly, RP11-498C9.15 targeted the largest number of signalling pathways that were found to be enriched by the global amount of RA-DEGs and that have already been associated with RA and RA–synoviocytes. Moreover, RP11-498C9.15 targeted the most highly connected genes in the RA interactome, thus suggesting its involvement in crucial gene regulation. These results indicate that, by modulating both microRNAs and gene expression, RP11-498C9.15 may play a pivotal role in RA pathogenesis.
Highlights
Rheumatoid arthritis (RA) is an autoimmune disease characterized by chronic inflammation of the joints with severe pain and swelling, joint damage and disability, which leads to joint destruction and loss of function [1]
We simultaneously profiled the expression of more than 540,000 human transcripts, including those ascribed to more than 50,000 long non-coding RNAs, in four peripheral blood mononuclear cells (PBMCs) samples from patients with clinically diagnosed RA symptoms, with the purpose of identifying lncRNAs potentially involved in RA pathogenesis
The functional classification by Gene Ontology of the 942 differentially expressed genes (DEGs) highlighted the modulation of transcripts that play a role in biological processes (BPs) strictly associated with RA, including apoptosis, cell proliferation, cell migration, inflammatory response, immune response, angiogenesis, extracellular matrix degradation and bone resorption
Summary
Rheumatoid arthritis (RA) is an autoimmune disease characterized by chronic inflammation of the joints with severe pain and swelling, joint damage and disability, which leads to joint destruction and loss of function [1]. Several genome-wide association studies have identified genetic variants that confer RA risk. These variants can explain less than 20% of susceptibility in RA. Several factors have been shown to contribute to the onset of the disease, such as genetic susceptibility, environmental factors including smoking, and epigenetic mechanisms [2]. LncRNAs are epigenetic regulators of gene expression and are involved in immune and inflammatory molecular networks. It has been demonstrated that they play a role in several autoimmune diseases [3]
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