MicroRNA‑140‑5p regulates the proliferation, apoptosis and inflammation of RA FLSs by repressing STAT3

Abstract

Ectopic expression of microRNA (miRNA) in rheumatoid arthritis (RA) fibroblast-like synoviocyte (RA FLS) is associated with the development of rheumatoid arthritis. The present study aimed to evaluate the effects of miRNA-140-5p (miR-140) on the properties of RA FLSs. It was found that miR-140 expression was decreased in 33 RA patients and extracted RA FLS samples, when compared to the corresponding healthy controls. Abnormally increased miR-140 expression in RA FLSs attenuated cell proliferation and increased cell apoptosis. Additionally, reduced pro-inflammatory cytokine production was observed in RA FLSs transfected with a miR-140 precursor. Furthermore, the 3'-UTR of the signal transducer and activator of transcription (STAT) 3 gene was identified as a target of miR-140. Notably, restoration of STAT3 expression rescued the regulatory effect of miR-140 on the proliferation, apoptosis and inflammatory cytokine production of RA FLSs. Therefore, the current findings indicated that miR-140 is a crucial modulator of both proliferation and apoptosis, shedding light on the etiology behind RA FLS viability, which is modulated by an interplay between miR-140 and STAT3 in the context of RA.

Circ_0001947 promotes cell proliferation, invasion, migration and inflammation and inhibits apoptosis in human rheumatoid arthritis fibroblast-like synoviocytes through miR-671-5p/STAT3 axis

“…Herein, we demonstrated that circ_0001947 silencing inhibited the dysfunction and inflammation of RA-FLSs by targeting miR-671-5p. Furthermore, overexpression of miR-671-5p inhibited RA-FLS growth, invasion, migration and inflammation and induced apoptosis by interacting with STAT3, which was reported to influence RA progression via acting as the target of miR-20a [ 31 ], miR-301a-3p [ 29 ] and miR-140-5p [ 37 ].…”

“…Signal transducer and activator of transcription 3 (STAT3) is a member of STAT family and the activation of STAT3 pathway is related to RA-FLS progression [ 32 ]. Zhu et al declared that miR-140-5p restrained the growth and inflammation and enhanced the apoptosis of RA-FLSs by targeting STAT3 [ 37 ]. Even so, the relation between miR-671-5p and STAT3 is unclear.…”

The Traditional Chinese Medicine Compound Huangqin Qingre Chubi Capsule Inhibits the Pathogenesis of Rheumatoid Arthritis Through the CUL4B/Wnt Pathway

“…In addition, FLS has the proliferation characteristics of stem cells, and the abnormal synovial hyperplasia may result from the compensatory regeneration of FLS caused by joint injury. In view of the key roles of FLS in the pathogenesis of RA, FLS is used as the research object in the study of RA pathological mechanisms and RA drug therapy (Zhu et al, 2021).…”

Synovial fibroblasts as potential drug targets in rheumatoid arthritis, where do we stand and where shall we go?

“…MicroRNAs (miRNAs) are small, non-coding gene silencing RNA molecules. A regulatory molecule, miR-140-5 p had decreased expression in the rheumatoid synovium in contrast to healthy synovial tissue and RA-FLS had a lower miR-140-5 p level compared with healthy FLS 40. The overexpression of miR-140-5 p in RA-FLS decreased survival and proliferation, while downregulating proinflammatory cytokine production, which all seemed to be dependent on the effect of miR-140-5 p on the expression of signal transducer and activator of transcription 3 (STAT3) 40.…”