Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease characterized by joint synovitis [
1,
2]. The clinical manifestations of RA includes joint swelling and pain caused by synovitis, cartilage destruction, joint space narrowing, joint stiffness, deformity and dysfunction, which are directly related to primary chronic low-grade inflammation [
3,
4]. RA affects 0.5-1 % of adults in developed countries and approximately 5–50 per 100,000 population in developing countries each year [
5]. RA onset is rare under the age of 15, but its incidence shows a steady increase with age until 80, with women 3–5 times more susceptible than men [
6]. The exact cause of RA is still unknown, but genetic factors, such as human leukocyte antigen-DR4 (
HLA-DR4) and other non-HLA genes including protein tyrosine phosphatase, non-receptor type 22 (
PTPN22) and peptidyl arginine deiminase, type IV (
PADI4), are suspected as major contributing factors [
7,
8]. Non-genetic factors also contribute significantly to RA and include Epstein-Barr virus (EBV) and Human Herpes Virus 6 (HHV-6) infections, hormonal infleunces, smoking, cold temperatures and trauma [
9,
10]. Previous studies show that loss of balance in proliferation and apoptosis of synovial fibroblast (SF) and abnormal secretion of various cytokines play key roles in RA pathogenesis. Multiple signaling pathways are activated during RA development [
11,
12]. Synovial tissue from RA patients shows infiltration by macrophages, T cells, and B cells, proliferation of cells lining the synovium, and production of inflammatory cytokines such as tumor necrosis factor α (TNFα) and interleukin-1β (IL-1β) [
13,
14]. Interestingly, inhibition of these cytokines ameliorates the clinical symptoms RA, strongly supporting the central role of cytokines in RA [
15]. Rheumatoid arthritis synovial fibroblast (RASFs) activity promotes joint destruction and increased expression of proinflammatory pathways and secretion of matrix-destructive enzymes is a common feature associated with the disease [
16]. Recent evidence suggests that miRNA dysregulation may contribute to RA etiopathogenesis and therefore, a better understanding of pathways regulated by miRNAs might shed light on RA pathogenesis and help identify effective RA treatments [
17].
MicroRNAs (miRNAs) are small, non-coding endogenous RNAs of 20 ~ 24 nucleotides in length and regulate gene expressions at the post-transcriptional level [
18]. MiRNAs bind to 3′ untranslated regions (3′ UTRs) of their target mRNAs and either block translation and/or promote target mRNA degradation [
19]. MiRNAs play important roles both in pathological and normal physiological processes such as embryonic development, energy homeostasis, metabolism of sugar and lipid as well as tumorigenesis [
20‐
23]. Several miRNAs modify cell behavior by regulating the nuclear factor-kB (NF-κB) pathway [
18]. For instance, miR-30e, miR-182, and miR-301a promote NF-κB activity to enhance tumor growth, invasiveness or angiogenesis [
24‐
26]. Joanna Stancz et al. observed dysregulated expression of miRNA miR-155 and miR-146a in synovial tissue, synovial fibroblasts and monocytes of rheumatoid joints [
16]. Previous studies showed that the miR-26 family, consisting of miR-26a and miR-26b, is down-regulated in several cancers such as hepatocellular carcinoma (HCC), melanoma, nasopharyngeal carcinoma and breast cancer [
27‐
31]. Although the cellular functions of miR-26b remain elusive, miR-26b inhibits NF-κB pathway in HCC cells by suppressing TAK1 and TAB3 expression, and down-regulation of miR-26b suppressed apoptosis in HCC cells [
18]. Thus far, the main role of miR-26b was described in cancers. However, due to the close relationship between cancer and inflammatory pathway, we investigated whether miR-26b influenced cell proliferation and inflammatory cytokine secretion in RASF cells and further sought to identify the underlying mechanisms.