LINC00837/miR-671-5p/SERPINE2 functional axis promotes pathological processes of fibroblast-like synovial cells in rheumatoid arthritis
CAO Zhoufang
WANG Yuan
WANG Mengna
SUN Yue
LIU Feifei
Abstract：Objective To investigate the regulatory effect of LINC00837/miR-671-5p/SERPINE2 functional axis on pathological processes of fibroblast-like synovial cells(FLS)in rheumatoid arthritis(RA).Methods RA-FLS were transfected with a LINC00837 overexpression plasmid(pcDNA3.1-LINC00837),a LINC00837 interference plasmid(siRNA-LINC00837),or their respective negative control plasmids(pcDNA3.1-NC and siRNA-NC).Dual luciferase was used to verify the targeting relationship between LINC00837 and miR-671-5p and between miR-671-5p and SERPINE2.RT-qPCR was used to detect the expression levels of LINC00837,miR-671-5p and SERPINE2 in normal FLS or the transfected cells,whose proliferation and migration abilities were assessed using Edu assay and scratch healing assay and by detecting the expression levels of Ki-67,PCNA,E-cadherin and N-cadherin with Western blotting.The changes in cellular secretion of the inflammatory cytokines(TNF-α,IL-17,IL-4 and IL-10)were examined using ELISA.Results Dual luciferase reporter gene assay showed that LINC00837 was capable of binding to the 3'-UTR of miR-671-5p,and the latter bound to the 3-UTR of SERPINE2 at specific binding sites between them.Compared with normal FLS,RA-FLS showed significantly increased expressions of LINC00837 and SERPINE2,lowered miR-671-5p expression and enhanced proliferation and migration abilities with increased expressions of pro-inflammatory cytokines and reduced expressions of anti-inflammatory cytokines.Transfection of RA-FLS with pcDNA-LINC00837 further enhanced cell proliferation and migration and the changes in the inflammatory cytokines,while transfection with si-LINC00837 produced the opposite changes.Conclusion RA-FLS have a LINC00837/miR-671-5p/SERPINE2 functional axis,which regulates cell proliferation,migration and secretion of inflammatory factors,and interventions targeting LINC00837 may provide a potential strategy to regulate the pathological processes in RA-FLS.
Keywords：rheumatoid arthritisfibroblast-like synovial cellsLINC00837proliferationmigrationinflammatory factors
Publication Date：2025-02-19
Online Publishing Date：2025-08-15(First online date of this platform, not the publication date of the document)
Pages：8( 371-378 )