Abstract
Accumulating studies have suggested that long non-coding RNAs (lncRNAs) have drawn more and more attention in rheumatoid arthritis (RA), which can function as competitive endogenous RNAs (ceRNAs) in inflammation and immune disorders. Previously, we have found that lncRNA HIX003209 is differentially expressed in RA. However, the precise mechanism of lncRNA HIX003209 in RA is still vague. We aim to elucidate the role and its targeted microRNA of lncRNA HIX003209 in RA as ceRNA. Significantly increased expression of lncRNA HIX003209 was observed in the peripheral blood mononuclear cells (PBMCs) from RA cases. It was positively associated with TLR2 and TLR4 in RA. Besides, peptidoglycan (PGN) and lipopolysaccharide (LPS) could enhance the expression of lncRNA HIX003209, which reversely promoted the proliferation and activation of macrophages through IκBα/NF-κB signaling pathway. Moreover, HIX003209 was involved in TLR4-mediated inflammation via targeting miR-6089 in macrophages. LncRNA HIX003209 functions as a ceRNA and exaggerates inflammation by sponging miR-6089 through TLR4/NF-κB pathway in macrophages, which offers promising therapeutic strategies for RA.
Highlights
Rheumatoid arthritis (RA) is a systemic autoimmune disease, the etiology of which remains largely unknown [1, 2]
The current study firstly provides evidence that long non-coding RNAs (lncRNAs) HIX003209 is involved in the pathogenesis of RA by enhancing macrophage-mediated inflammatory response via TLR2/TLR4
LncRNA HIX003209 can function as a competitive endogenous RNAs (ceRNAs) by effectively binding to miR-6089, which restores the expression of TLR4 and the activation of downstream signaling molecule NFκB in macrophages
Summary
Rheumatoid arthritis (RA) is a systemic autoimmune disease, the etiology of which remains largely unknown [1, 2]. RA Patients usually have decreased quality of life due to progressive disability and systemic complications [3, 4]. It has been well-documented that genetics and environmental factors, such as smoking, are associated with the development of RA [4]. Apart from autoimmune, uncontrolled and systemic inflammation lead to joint damage, disability, decreased life quality, and increased risk of cardiovascular comorbidities among RA patients. Accumulating studies have suggested that non-coding RNAs, long non-coding RNAs (lncRNAs), have been revealed in inflammation, cancer and autoimmune [5, 6].
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