Long noncoding RNAs expression profile and functional networks in rheumatoid arthritis

Abstract

The modifying effects of long noncoding RNAs (lncRNAs) in rheumatoid arthritis (RA) recently have drawn much attention; however, the underlying mechanisms remain largely unknown. Herein, we aim to investigate the expression profile of lncRNAs in RA and identify promising targets for RA diagnosis and treatment. Microarray screening and real-time PCR of lncRNAs were performed by use of serum samples from 3 RA patients and 3 healthy controls. Significantly differentially expressed lncRNAs were verified in serum samples from 43 RA patients and 40 healthy controls by real-time PCR. We found that there were 73 up-regulated and 61 down-regulated lncRNAs as well as 128 up-regulated and 37 down-regulated mRNAs in serum samples of RA patients. Validation in RA clinical samples indicated 5 of these lncRNAs were significantly up-regulated including RNA143598, RNA143596, HIX0032090, IGHCgamma1, and XLOC_002730. Significant association was observed between these lncRNAs and the disease course, erythrocyte sedimentation rate (ESR), rheumatoid factor (RF) as well as anti-cyclic citrullinated peptide (anti-CCP) antibody. Additionally, 55 of the differentially expressed mRNAs were associated with 41 lncRNAs and were involved in signaling pathways of toll like receptors (TLRs), nuclear factor-kappa B (NF-κB), and cytokine, especially the IRF3/IRF7 mediated signaling transduction. Our study firstly shows the specific profile of lncRNAs in the serum of RA patients and potential signaling pathways involved in RA pathogenesis, which may provide novel targets for the diagnosis and treatment of patients with RA.

lncRNA IGHCγ1 Acts as a ceRNA to Regulate Macrophage Inflammation via the miR-6891-3p/TLR4 Axis in Osteoarthritis

“…Those differentially expressed lncRNAs are specific in OA and may be used as diagnostic or therapeutic targets in the future. lncRNA IGHCγ1 is an aberrantly expressed lncRNA in inflammatory arthritis [15]. However, the precise role of lncRNA IGHCγ1 in OA is not fully elucidated.…”

“…Available studies have revealed a variety of miRNAs are aberrantly expressed in OA patients [13,14]. Our previous study has shown that lncRNA IGHCγ1 (also called IGHCgamma1) is involved in regulating arthritis [15], but the altering effect of lncRNA IGHCγ1 in OA is unknown. With development in bioinformatics and molecular biology techniques, the ceRNA mechanism based on interactions among lncRNA, miRNA, and mRNA has been extensively elucidated [16,17].…”

The Role of Long Non-coding RNAs in the Pathogenesis of RA, SLE, and SS

“…Besides cells, serum samples also be used for identification of RA-related lncRNAs. To identify lncRNAs associated with RA, Xu et al investigated the expression profile of lncRNAs in serum samples from 3 RA patients and 3 health controls by microarray and then verified the interested lncRNAs in 43 RA patients and 40 healthy controls by quantitative RT-PCR ( 25 ). This study has identified 5 significantly up-regulated lncRNAs in RA as compared with controls, including RNA143598, RNA143596, HIX0032090, IGHCgamma1 and XLOC_002730.…”

“…This study has identified 5 significantly up-regulated lncRNAs in RA as compared with controls, including RNA143598, RNA143596, HIX0032090, IGHCgamma1 and XLOC_002730. Moreover, these lncRNAs are positively correlated with some immunological and clinical features of RA, including rheumatoid factor (RF), erythrocyte sedimentation rate (ESR), anti-cyclic citrullinated peptide (anti-CCP) antibody and disease course ( 25 ).…”

“…lncRNAs are actively involved in the regulation of many biological processes, including development and function of immune cells. Recently, a body of evidence has been accumulated showing that lncRNAs are involved in the pathogenesis of rheumatoid diseases, such as SS, SLE and RA ( 23 – 25 ).…”