Rheumatoid arthritis fibroblast-like synoviocytes maintain tumor-like biological characteristics through...

Altered phenotype of Fibroblast-like synoviocyte(FLS) is an important cause of the pathogenesis and progression of rheumatoid arthritis(RA), but the specific mechanism causing this change has not yet been fully explained. The exact mechanism by which the biological properties of FLS change in RA is still unclear. microRNAs (miRNAs) have been shown to affect changes in the biological properties of RA-FLS, but the critical miRNAs remain to be discovered. Thus, we first used miRNA microarray and WGCNA to confirm the RA-FLS miRNA landscape and establish their biological functions via network analyses at the system level, as well as to provide a platform for modulating the overall phenotypic effects of RA-FLS.

We enrolled a total of 3 patients with RA and 3 healthy participants, constructed a network analysis of via miRNA microarray and RNA-sequencing. Furthermore, the coexpression analyses of miR-7 and ciRS-7 were verified by siRNA transfection, overexpression and qPCR analyses. Finally, we evaluated the effects of adjusting the expression levels of miR-7 and ciRS-7 on RA-FLS, respectively.

We identified distinct miRNA features in RA-FLS, including miR-7, which was significantly lower expressed. Furthermore, we discovered the negative regulatory relationship between ciRS-7 and miR-7 in RA-FLS. Finally, we overexpressed miR-7 in RA-FLS and discovered that miR-7 inhibited RA-FLS hyperproliferation, migration, invasion, and apoptosis, whereas ciRS-7 overexpression reversed these effects.

The results indicate that the dysregulation of miR-7 in FLS may be involved in the pathological processes of RA and that ciRS-7 induced the suppression of tumor-like biological characters of RA-FLS via modulation of miR-7. These findings help us understand the essential roles of a regulatory interaction between ciRS-7 and miR-7 mediating disease activity of RA, and will facilitate to develop potential intervention target for RA.