MicroRNA-101-3p inhibits fibroblast-like synoviocyte proliferation and inflammation in rheumatoid arthritis by targeting PTGS2

Abstract

Objective: Rheumatoid arthritis (RA) is the most frequently occurring inflammatory arthritis. The present study was performed to characterize the role of microRNA-101-3p (miR-101-3p) and prostaglandin-endoperoxide synthase 2 (PTGS2) in inflammation and biological activities of fibroblast-like synoviocytes (FLSs) in RA. Methods: Initially, miR-101-3p and PTGS2 expression in RA tissues of RA patients and RA rats was detected by qRT-PCR and Western blot analysis. Rat model of type II collagen-induced arthritis (CIA) was adopted to simulate RA, followed by injection of miR-101-3p mimics or siRNA against PTGS2. Next, the apoptosis in synovial tissue and the levels of tumor necrosis factor (TNF)-α, IL-1β and IL-6 were identified. Subsequently, FLSs in RA (RA-FLSs) were isolated, after which in vitro experiments were conducted to analyze cell proliferation, apoptosis, migration and invasion upon treatment of up-regulated miR-101-3p and silenced PTGS2. Furthermore, the relationship of miR-101-3p and PTGS2 was determined by bioinformatics prediction and luciferase activity assay. Results: We identified poorly expressed miR-101-3p and highly expressed PTGS2 in synovial tissues of RA patients and RA rats, which showed reduced synoviocyte apoptosis and enhanced inflammation. In response to miR-101-3p mimics and si-PTGS2, the RA-FLSs were observed with attenuated cell proliferation, migration and invasion, corresponding to promoted apoptosis. Down-regulation of PTGS2 could rescue the effect of inhibited miR-101-3p in synovial injury and phenotypic changes of FLS in RA rats. Notably, miR-101-3p was found to negatively regulate PTGS2. Conclusion: Taken together, miR-101-3p reduces the joint swelling and arthritis index in RA rats by down-regulating PTGS2, as evidenced by inhibited FLS proliferation and inflammation.

Overexpression of miR-146b-5p Ameliorates Neonatal Hypoxic Ischemic Encephalopathy by Inhibiting IRAK1/TRAF6/TAK1/NF-αB Signaling

“…8 miR-101-3p is dysregulated and plays a role in synovial fibroblast-like cells in patients with rheumatoid arthritis. 9 Interestingly, many miRNAs have been shown to have regulatory effects on HIE. For instance, miR-499-5p exhibits neuroprotective effects on HIE in neonatal rats by blocking C-reactive protein.…”

Inhibition of miR‑101‑3p protects against sepsis‑induced myocardial injury by inhibiting MAPK and NF‑κB pathway activation via the upregulation of DUSP1

“…As a mature form of miR-101, decreased levels of miR-101-3p have been shown to exert tumor suppressor functions in numerous malignant tumors, and to regulate proliferation, invasion and metastasis ( 20 , 21 ). However, to the best of our knowledge, the role of miR-101-3p in inflammatory diseases has been rarely reported.…”

“…In non-tumor diseases, miR-101-3p has been shown to be significantly upregulated in the plasma of patients with adult onset Still's disease (AOSD) and to positively correlate with the expression of inflammatory mediators ( 20 ). Moreover, miR-101-3p also affects other inflammation-related diseases, such as rheumatoid arthritis ( 21 ) and heart transplant recipients with histologically-verified acute cellular rejection ( 22 ). However, to the best of our knowledge, there are limited studies available investigating the effects of miR-101-3p on the inflammatory response post-SIC.…”

Functional interaction between long non‐coding RNA and microRNA in rheumatoid arthritis

“…Zhou et al 51 demonstrated that miR‐27b directly inhibits HIPK2 expression that would lead to chondrocyte apoptosis and, thus, ameliorate the development of RA. Recently, Wei et al 52 ascertained that miR‐101‐3p reduces joint swelling and the rheumatoid factors in rats with RA by downregulating PTGS2, as evidenced by inhibited FLS proliferation and inflammation. Studies have verified that miRNAs are expressed in both the synovial tissue and the circulating blood in patients with RA, meaning that miRNA may serve as a biomarker for RA.…”