SPTBN1 attenuates rheumatoid arthritis synovial cell proliferation, invasion, migration and inflammatory response by binding to PIK3R2

BACKGROUND: As an autoimmune systemic disorder, rheumatoid arthritis (RA) features chronic inflammation as well as synovial infiltration of immune cells. This study was designed with the purpose of discussing the hidden mechanism of SPTBN1 and exploring favorable molecular‐targeted therapies. METHODS: With the application of RT‐qPCR and western blot, the expressions of SPTBN1 and PIK3R2 before or after transfection were estimated. Besides, Cell Counting Kit‐8, Edu, wound healing, transwell, enzyme‐linked immunosorbent assay, and TUNEL were adopted for the evaluation of the viability, proliferation, migration, invasion, inflammatory response, and apoptosis of fibroblast‐like synoviocyte (FLS). In addition, the interaction of SPTBN1 and PIK3R2 was testified by applying immunoprecipitation (IP) and western blot was utilized for the assessment of migration‐, apoptosis‐, and PI3K/AKT signal‐related proteins. RESULTS: It was discovered that SPTBN1 declined in RA synovial cells and its overexpression repressed the proliferation, migration, invasion, and inflammation of RA‐FLSs but promoted apoptosis. IP confirmed that SPTBN1 could bind to PIK3R2 in FLSs. To further figure out the hidden mechanism of SPTBN1 in RA, a series of functional experiments were carried out and the results demonstrated that the reduced expressions of MMP2, MMP9, IL‐8, IL‐1β, IL‐6, and Bcl2 as well as increased levels of Bax and cleaved caspase3 in SPTBN1‐overexpressed RA‐FLSs were reversed by PIK3R2 depletion, revealing that SPTBN1 repressed the migration and inflammation and promoted the apoptosis of RA‐FLSs via binding to PIK3R2. Results obtained from western blot also revealed that PIK3R2 interference ascended the contents of p‐PI3K and p‐AKT in SPTBN1‐overexpressed RA‐FLSs, implying that SPTBN1 repressed PI3K/AKT signal in RA via PIK3R2. DISCUSSION: SPTBN1 alleviated the proliferation, migration, invasion, and inflammation in RA via interacting with PIK3R2.