Citrullinated IGF2BP1 promotes rheumatoid synovial aggression via increasing the mRNA stability of SEMA3D

Protein citrullination modification plays a pivotal role in the pathogenesis of rheumatoid arthritis (RA), and anti-citrullinated protein antibodies (ACPAs) are extensively employed for clinical diagnosis of RA. However, there remains limited understanding regarding specific citrullinated proteins and their implications in the progression of RA. In this study, we screened and verified insulin-like growth factor-2 mRNA binding protein 1 (IGF2BP1) as a novel citrullinated protein and R167 was the primary citrullination site. Functional verification showed that citrullination at the R167 site of IGF2BP1 promoted the proliferation, migration and invasion of RA fibroblast-like synoviocytes (RA-FLSs). To further explore the specific downstream target of citrullinated IGF2BP1, RNA sequencing was conducted in this study. Overall design: To identified the downstream target gene of citrliinated IGF2BP1, IGF2BP1 was firstly knocked down in RA-FLSs, then rescued with a mutant IGF2BP1 plasmid with R167K point mutaion, or a wildtype IGF2BP1 plasmid. (WUT= IGF2BP1 R167K group, NC= IGF2BP1 wildtype group, n=3 per group.)