Non-coding RNAs in Rheumatoid Arthritis: From Bench to Bedside

Wang, Jinghua; Yan, Shushan; Yang, Jinghan; Lu, Hongying; Xu, Dongmei; Wang, Zengyan

doi:10.3389/fimmu.2019.03129

Cited by 110 publications

(86 citation statements)

References 99 publications

(118 reference statements)

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“…Identification of aberrantly expressed lncRNAs in RA and exploration of the underlying molecular mechanisms will offer a new direction to understand the pathogenesis of RA ( 52 ). To date, LncRNA H19, Hotair, lincRNA-p21, C5T1, LOC100652951, and LOC100506036 have been verified to be dysregulated in T cells, PBMCs, exosomes, and synovial cells, which are associated with inflammation and immune reaction in RA ( 52 ). The WAKMAR2 has been proven as an important regulator in the healing of skin wound and its deficiency may contribute to the pathogenesis of chronic wounds ( 53 ).…”

Section: Discussionmentioning

confidence: 99%

Therapeutic Effects of (5R)-5-Hydroxytriptolide on Fibroblast-Like Synoviocytes in Rheumatoid Arthritis via lncRNA WAKMAR2/miR-4478/E2F1/p53 Axis

et al. 2021

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Rheumatoid arthritis (RA) is an autoimmune disease. Fibroblast-like synoviocytes (FLS) serve a major role in synovial hyperplasia and inflammation in RA. (5R)-5-hydroxytriptolide (LLDT-8), a novel triptolide derivative, shows promising therapeutic effects for RA and is now in phase II clinical trials in China. However, the underlying mechanism of LLDT-8 is still not fully understood. Here, we found that LLDT-8 inhibited proliferation and invasion of RA FLS, as well as the production of cytokines. Microarray data demonstrated that LLDT-8 upregulated the expression of long non-coding RNA (lncRNA) WAKMAR2, which was negatively associated with proliferation and invasion of RA FLS, as well as the production of pro-inflammatory cytokines. Knockdown of WAKMAR2 abolished the inhibitory effects of LLDT-8 on RA FLS. Mechanistically, WAKMAR2 sponged miR-4478, which targeted E2F1 and downstreamed p53 signaling. Rescue experiments indicated that the inhibitory effects of LLDT-8 on RA FLS were dependent on WAKMAR2/miR-4478/E2F1/p53 axis.

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Section: Discussionmentioning

confidence: 99%

Therapeutic Effects of (5R)-5-Hydroxytriptolide on Fibroblast-Like Synoviocytes in Rheumatoid Arthritis via lncRNA WAKMAR2/miR-4478/E2F1/p53 Axis

et al. 2021

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“…Noncoding RNAs are involved in the autoimmunity and inflammation that play important roles in RA development [ 7 ]. Circular RNAs (circRNAs) are a type of closed noncoding RNAs which bind with microRNA (miRNA) to reduce miRNA activity, subsequently increasing mRNA stability, which have key roles in aging-related diseases, including RA [ 8 ].…”

Section: Introductionmentioning

confidence: 99%

Circ-AFF2/miR-650/CNP axis promotes proliferation, inflammatory response, migration, and invasion of rheumatoid arthritis synovial fibroblasts

Jiang

Hou

2021

J Orthop Surg Res

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Background Circular RNAs (circRNAs) are associated with rheumatoid arthritis (RA) development. The purpose of this study is to explore the function and mechanism of circRNA fragile mental retardation 2 (circ-AFF2) in the processes of rheumatoid arthritis fibroblast-like synoviocytes (RAFLSs). Methods Circ-AFF2, microRNA (miR)-650, and 2′,3′-cyclic nucleotide 3′-phosphodiesterase (CNP) levels were determined in synovial tissues of RA and RAFLSs by quantitative reverse transcription polymerase chain reaction or Western blotting. Cell proliferation, inflammatory response, apoptosis, caspase3 activity, migration, invasion, and epithelial-mesenchymal transition (EMT) were investigated using Cell Counting Kit-8 (CCK-8), enzyme-linked immunosorbent assay (ELISA), flow cytometry, Transwell, and Western blotting analyses. Dual-luciferase reporter, RNA immunoprecipitation (RIP), and pull-down assays were performed to assess the binding relationship. Results Circ-AFF2 expression level was enhanced in synovial tissues of RA and RAFLSs. Circ-AFF2 overexpression facilitated cell proliferation, inflammatory response, migration, invasion, and EMT and repressed apoptosis in RAFLSs. Circ-AFF2 downregulation played an opposite role. Circ-AFF2 targeted miR-650, and miR-650 downregulation reversed the effect of circ-AFF2 interference on RAFLS processes. CNP was targeted by miR-650, and circ-AFF2 increased CNP expression by regulating miR-650. MiR-650 overexpression constrained cell proliferation, inflammatory response, migration, invasion, and EMT and contributed to apoptosis by decreasing CNP in RAFLSs. Conclusion Circ-AFF2 promoted proliferation, inflammatory response, migration, and invasion of RAFLSs by modulating the miR-650/CNP axis.

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“…Emerging evidence has indicated significant roles of non‐coding RNAs (ncRNAs) in inflammation and autoimmune regulation, mainly including long non‐coding RNAs (lncRNAs), microRNAs (miRNAs) and circular RNAs (Wang et al., 2019). Abnormal expression of lncRNAs and miRNAs has been revealed in RA‐FLSs and is closely linked with RA‐FLS proliferation and cytokine production as well as RA pathogenesis (Karami et al., 2020).…”

Section: Introductionmentioning

confidence: 99%

Inhibitory role of long non‐coding RNA OIP5‐AS1 in rheumatoid arthritis progression through the microRNA‐448–paraoxonase 1–toll‐like receptor 3–nuclear factor κB axis

Qing

Liu

2020

Experimental Physiology

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Rheumatoid arthritis (RA) is an autoimmune disorder with dysregulation of long noncoding RNAs (lncRNAs) possibly involved. This study aimed to inquire into the roles of lncRNA OIP5-AS1 in RA progression. A rat model of RA was induced. Overexpression of OIP5-AS1 was introduced in the model rats, and the changes in paw swelling, RA severity and the inflammatory factors interleukin (IL)-1β, IL-10, IL-6 and tumour necrosis factor α were measured. Fibroblast-like synoviocytes (FLSs) from RA patients were collected for in vitro experiments. A gain-and loss-of function study of OIP5-AS1, miR-448 and paraoxonase 1 (PON1) was performed to explore their roles in RA-FLS growth, apoptosis and inflammation. A toll-like receptor 3 (TLR3)-specific agonist, polyinosine-polycytidylic acid, or a nuclear factor κB (NF-κB)-specific antagonist, QNZ, was administrated in RA-FLSs. Consequently, overexpression of OIP5-AS1 reduced the symptom severity and the levels of inflammatory factors in RA rats. OIP5-AS1 could bind to miR-448 to up-regulate PON1 expression. Further overexpression of miR-448 reversed the effects of OIP5-AS1, while overexpression of PON1 inhibited RA-FLS growth and inflammation. In addition, TLR3 activation promoted RA progression. To conclude, this study evidenced that lncRNA OIP5-AS1 may mitigate RA progression through the miR-448-PON1 axis and through the inactivation of the TLR3-NF-κB signalling pathway. K E Y W O R D S long non-coding RNA OIP5-AS1, microRNA-448, paraoxonase 1, rheumatoid arthritis, TLR3/NF-κB signalling pathway 1 INTRODUCTION Rheumatoid arthritis (RA) is a common chronic autoimmune disorder that features severe synovial proliferation, inflammation, rheumatoid pannus formation and autoantibody production (Hoxha, 2018). This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

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Non-coding RNAs in Rheumatoid Arthritis: From Bench to Bedside

Cited by 110 publications

References 99 publications

Therapeutic Effects of (5R)-5-Hydroxytriptolide on Fibroblast-Like Synoviocytes in Rheumatoid Arthritis via lncRNA WAKMAR2/miR-4478/E2F1/p53 Axis

Therapeutic Effects of (5R)-5-Hydroxytriptolide on Fibroblast-Like Synoviocytes in Rheumatoid Arthritis via lncRNA WAKMAR2/miR-4478/E2F1/p53 Axis

Circ-AFF2/miR-650/CNP axis promotes proliferation, inflammatory response, migration, and invasion of rheumatoid arthritis synovial fibroblasts

Inhibitory role of long non‐coding RNA OIP5‐AS1 in rheumatoid arthritis progression through the microRNA‐448–paraoxonase 1–toll‐like receptor 3–nuclear factor κB axis

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