lncRNA XIST调控miR-125b及JAK2/STAT3通路对类风湿关节炎滑膜细胞生物学功能的影响及分子机制OA

Objective:To investigate the effect and molecular mechanism of lncRNA XIST on the biological functions of rheumatoid arthritis(RA)fibroblast-like synoviocytes(FLSs)by regulating miR-125b and the JAK2/STAT3 pathway.Methods:RA-FLS models with XIST overexpression(ov-XIST)and silencing(si-XIST)were constructed,with corre-sponding negative controls(EV Ctrl and si-NC)were set up.CCK-8 assay,flow cytometry,Transwell assay,and ELISA were used to detect cell proliferation,apoptosis,invasion,and secretion of inflammatory factors(TNF-α,IL-6,IL-1β).qRT-PCR and Western blot were employed to determine the expression levels of XIST,miR-125b,and proteins related to the JAK2/STAT3 pathway;a dual-luciferase reporter assay was performed(with verification of miR-125b transfection ef-ficiency)to verify the targeting relationship between XIST and miR-125b;the optimal intervention concentration of AG490 was determined via concentration gradient screening,followed by intervention experiments involving XIST overex-pression combined with miR-125b inhibitor or the JAK2/STAT3 pathway inhibitor(AG490)to confirm the role of the pathway,and an AG490-alone intervention group set up to clarify its own effect.Results:In the ov-XIST group,RA-FLS proliferation,invasion,and inflammatory factor secretion were enhanced,while apoptosis was reduced,whereas the si-XIST group showed the opposite results.XIST had a targeted binding to miR-125b,and XIST overexpression downregulated miR-125b and indirectly activated the JAK2/STAT3 path-way;functional rescue experiments showed that inhibiting miR-125b could enhance the pro-activation effect of XIST,while AG490 could reverse this effect,and AG490 itself had no significant effect on the core biological functions of RA-FLSs.Conclusion:lncRNA XIST activates the JAK2/STAT3 pathway by sponging miR-125b,promotes abnormal activation of RA-FLSs,participates in the pathological process of RA,and serves as a potential target for RA treatment.