MLL1 knockdown in RA-fibroblast-like synoviocytes significantly suppressed their proliferation and invasion, highlighting a novel regulatory axis involving KLF7 and USP7.
Does MLL1 knockdown reduce proliferation and invasion in fibroblast-like synoviocytes from rheumatoid arthritis patients?
The study identifies a novel MLL1/KLF7/USP7 regulatory axis that drives synovial fibroblast invasion in rheumatoid arthritis, highlighting a potential new therapeutic target.
Absolute Event Rate: 0% vs 0%
This study aims to elucidate the role of mixed lineage leukemia 1 (MLL1) in regulating the invasion of fibroblast-like synoviocytes (FLSs) in rheumatoid arthritis (RA). RA-FLSs and HC-FLSs were isolated and cultured from synovial tissues of RA patients and healthy controls (HC). MLL1 knockdown was achieved in RA-FLSs using shRNA transfection. The expression of MLL1, Krüppel-like factor 7 (KLF7), and ubiquitin carboxyl-terminal hydrolase 7 (USP7) was assessed via quantitative real-time polymerase chain reaction (qRT-PCR) or Western blot. Cell proliferation and invasion were evaluated using cell counting kit-8 (CCK-8) and Transwell assays. Chromatin immunoprecipitation (ChIP) assays were conducted to determine the enrichment of MLL1 and histone H3 lysine 4 trimethylation (H3K4me3) at the KLF7 promoter and the binding of KLF7 to the USP7 promoter. A dual-luciferase assay was used to validate the transcriptional activation of USP7 by KLF7. Results demonstrated that MLL1 was significantly overexpressed in RA-FLSs, and its inhibition suppressed FLS proliferation and invasion. Mechanistically, MLL1 promoted KLF7 transcription through H3K4me3 modification, and KLF7 subsequently upregulated USP7 expression. These findings reveal a novel MLL1/KLF7/USP7 regulatory axis that facilitates RA-FLS invasion and may represent a potential therapeutic target in RA.
Cen et al. (Sat,) reported a other. MLL1 knockdown in RA-fibroblast-like synoviocytes significantly suppressed their proliferation and invasion, highlighting a novel regulatory axis involving KLF7 and USP7.