The Expression of Non-Coding RNAs and Their Target Molecules in Rheumatoid Arthritis: A Molecular Basis for Rheumatoid Pathogenesis and Its Potential Clinical Applications

Abstract

Rheumatoid arthritis (RA) is a typical autoimmune-mediated rheumatic disease presenting as a chronic synovitis in the joint. The chronic synovial inflammation is characterized by hyper-vascularity and extravasation of various immune-related cells to form lymphoid aggregates where an intimate cross-talk among innate and adaptive immune cells takes place. These interactions facilitate production of abundant proinflammatory cytokines, chemokines and growth factors for the proliferation/maturation/differentiation of B lymphocytes to become plasma cells. Finally, the autoantibodies against denatured immunoglobulin G (rheumatoid factors), EB virus nuclear antigens (EBNAs) and citrullinated protein (ACPAs) are produced to trigger the development of RA. Furthermore, it is documented that gene mutations, abnormal epigenetic regulation of peptidylarginine deiminase genes 2 and 4 (PADI2 and PADI4), and thereby the induced autoantibodies against PAD2 and PAD4 are implicated in ACPA production in RA patients. The aberrant expressions of non-coding RNAs (ncRNAs) including microRNAs (miRs) and long non-coding RNAs (lncRNAs) in the immune system undoubtedly derange the mRNA expressions of cytokines/chemokines/growth factors. In the present review, we will discuss in detail the expression of these ncRNAs and their target molecules participating in developing RA, and the potential biomarkers for the disease, its diagnosis, cardiovascular complications and therapeutic response. Finally, we propose some prospective investigations for unraveling the conundrums of rheumatoid pathogenesis.

Functional Interactions Between lncRNAs/circRNAs and miRNAs: Insights Into Rheumatoid Arthritis

“…RA is a multifactorial and heterogeneous disease; accumulating evidence have documented that genetics is one of its key factors (7). Recently, the influences of environmental factors and geneenvironment interactions have been revealed, providing new clues on disease pathogenesis (8).…”

Recent Advances in Understanding the Pathogenesis of Rheumatoid Arthritis: New Treatment Strategies

“…It is mainly concerned with the changes in gene expression and phenotypes of cells that are not related to changes in DNA sequence, which adds new quality and a whole new dynamic to the overview of gene expression. Epigenetic phenomena, such as DNA methylation, chromatin remodeling, post-translational histone modifications, and non-coding RNAs [ 289 , 290 , 291 ], are of fundamental importance in regulating gene expression in medicine, various diseases, and numerous processes such as cell proliferation and differentiation, development, cardiovascular diseases, diabetes, autoimmune diseases, and cancer [ 292 , 293 , 294 , 295 ].…”

Circulating Vitreous microRNA as Possible Biomarker in High Myopic Eyes with Macular Hole

“…In the current study, we investigated the miRNA profile in the vitreous of MH and high myopic MH using real-time quantitative polymerase chain reaction (PCR)-based TaqMan microRNA arrays, and we determined the correlation between the expression level of each miRNA in the vitreous and axial length. Furthermore, since recent reports have demonstrated that microRNAs have pathogenic, therapeutic, and diagnostic roles in inflammatory disorders [ 28 , 29 ], we evaluated the vitreous inflammatory cytokine signature in high myopic MH eyes.…”