Received: 27 February 2018 | Accepted: 13 June 2018 DOI: 10.1002/jcp.26911 REVIEW ARTICLE Implications of the noncoding RNAs in rheumatoid arthritis pathogenesis Mohammad Javad Mousavi 1,2,3 | Ahmadreza Jamshidi 1 | Arvind Chopra 4 | Saeed Aslani 1 | Massoomeh Akhlaghi 1 | Mahdi Mahmoudi 1 1 Rheumatology Research Center, Tehran University of Medical Sciences, Tehran, Iran 2 Department of Hematology, Faculty of Allied Medicine, Bushehr University of Medical Sciences, Bushehr, Iran 3 Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran 4 Centre for Rheumatic Diseases, Pune, Maharashtra, India Correspondence Mahdi Mahmoudi, PhD, Rheumatology Research Center, Shariati Hospital, Kargar Ave., Tehran 1411713137, Iran. Email: mahmoudim@tums.ac.ir Arvind Chopra, MD, Center for Rheumatic Diseases, Camp St., Pune, Maharashtra 411001, India. Email: crdp@vsnl.net; arvindchopra60@hotmail.com Funding information Tehran University of Medical Sciences and Health Services, Grant/Award Number: 96‐03‐41‐36485 Epigenetics refers to a set of regulatory mechanisms that affect gene expression, while the original sequence of the DNA remains unchanged. Because the advance of noncoding RNAs (ncRNAs), the role of microRNAs (miRNAs) has been gradually highlighted in the regulation of numerous cellular processes. A bulk of studies has identified that ncRNAs might be divided into several subtypes. On the one hand, investigations have disclosed the role of these molecules in normal physiological conditions of the cells. On the other hand, there is sufficient evidence that ncRNAs participate in the pathogenesis of diseases. Through this review article, we attempted to gain a comprehensive understanding of the role of ncRNAs, long ncRNAs, miRNAs, and other subtypes in pathogenesis, diagnosis, and treatment of rheumatoid arthritis (RA). Research demonstrated aberrant expression of several miRNAs in various cell and tissue types of patients with RA in comparison to the healthy individuals as well as in animal studies. Furthermore, plausible molecular mechanisms of alterations in ncRNAs expression has been discussed in causing the disease state. These alterations seem promising to be used as biomarkers in RA diagnosis. Alternately, they might be targeted by drugs to interrupt inflammation and other disease complications to treat patients with RA. KEYWORDS biomarker, epigenetics, inflammation, long noncoding RNA (lncRNA), microRNAs (miRNA), noncoding RNA (ncRNAs), rheumatoid arthritis (RA) 1 | INTRODUCTION Rheumatoid arthritis (RA) is a chronic and severe inflammatory disease, which is characterized by a progressive bone, cartilage, and joint destruction. Approximately 1% of the worldwide population is affected by RA, making the disease one of the most prevalent autoimmune disorders around the world (Firestein, 2003; Gibofsky, 2012). The prevalence in siblings is reported to be two‐ to fourfold higher than others (Seldin, Amos, Ward, & Gregersen, 1999). This autoimmune disorder results in various irreversible symptoms including joint pain, stiffness, and swelling. One of the most common features of this disease is the thickening and hyperplasia of synovial line alongside with infiltration of inflammatory cells and synovial fibroblasts (Lipsky, 2007). The disease involves large and small joints in organs such as shoulder joints, fingers, elbows, knees, and ankles (Aletaha et al., 2010). The occurred systemic effects particularly results in a persistent synovial inflammation, finally leading to a severe disability and early death (Aletaha et al., 2010; Majithia & Geraci, 2007). Despite the tremendous efforts, designing a definite cure for RA has not yet been developed (Singh et al., 2012). Besides activated B lymphocytes and plasma cells (Edwards et al., 2004), other immune‐related cells including T helper (Th) 1, Th17 (Steinman, 2010), macrophages, and other innate effector cells are regularly found in inflamed synovia of patients with RA (Firestein, 2003). These cells play critical roles in the activation of synoviocytes and chondrocytes, destruction of cartilage and bone, and the J Cell Physiol. 2018;1–13. wileyonlinelibrary.com/journal/jcp © 2018 Wiley Periodicals, Inc., A Wiley Company | 1