Abstract
BACKGROUND: N6-methyladenosine (m6A) methylation modification plays an essential role in the molecular pathogenesis of preeclampsia (PE). This study aimed to explore m6A modification in in vitro PE model, involving RNA binding motif protein 15 (RBM15) and FBJ murine osteosarcoma viral oncogene homolog B (FOSB). METHODS: PE was induced by lipopolysaccharide (LPS) in HTR8/SVneo cells. Real-time quantification PCR was used for mRNA detection and Western blotting was used for protein detection. Cell cytokines were examined using enzyme-linked immunosorbent assay. Cell functions were evaluated using EdU assay, flow cytometry, and transwell assay. RNA immunoprecipitation assay and dual-luciferase reporter assay were utilized for validating molecular interaction. RESULTS: FOSB was highly expressed in placenta tissues from PE patients. Functionally, LPS-induced inflammation, proliferation inhibition, cell apoptosis and migration suppression were significantly abolished following FOSB knockdown. RBM15 upregulated FOSB expression via inducing m6A modification of FOSB mRNA. YTH N6-methyladenosine RNA-binding protein 1 (YTHDF1) acted as an m6A reader protein, and RBM15 enhanced the binding between YTHDF1 and FOSB. RBM15 knockdown relieved LPS-caused trophoblast cell injury by inhibiting FOSB. CONCLUSION: These results collectively suggested that RBM15 accelerated trophoblast cell dysfunction via mediating m6A modification of FOSB mRNA through the identification by YTHDF1.