MicroRNA-449 targets histone deacetylase 1 to regulate the proliferation, invasion, and apoptosis of synovial fibroblasts in rheumatoid arthritis

BACKGROUND Rheumatoid arthritis (RA) is a chronic joint disease. The study aimed to explore the effects of microRNA (miR)-449 and histone deacetylase 1 (HDAC1) on the proliferation, invasion, and apoptosis of synovial fibroblasts in rheumatoid arthritis. METHODS Synovial tissue was collected from 20 patients with RA and 20 patients with osteoarthritis (OA) who underwent joint replacement surgery. RA synovial fibroblasts (RASFs) and OA synovial fibroblasts (OASFs) were isolated and cultured. Real-time quantitative PCR was used to detect the expression levels of miR-449 and HDAC1 in synovial tissues and cells. Western blot was performed to detect the cellular expression levels of HDAC1 protein, and apoptosis and invasion-related proteins. The proliferation, invasion, and apoptosis of RASFs were detected by MTT assay, Transwell assay, and flow cytometry. The dual-luciferase reporter gene was used to test the targeting relationship between inflammatory miR-449 and HDAC1. RESULTS Compared with normal synovial tissue and OASFs, the levels of HDAC1 messenger RNA in RA synovial tissue and RASF cells were significantly increased (P<0.01), while the expression levels of miR-449 were significantly decreased (P<0.01). The dual-luciferase reporter gene experiment confirmed that miR-449 could specifically bind to the 3' untranslated region of HDAC1 to inhibit its luciferase activity (P<0.05). HDAC1 inhibition or miR-449 overexpression significantly inhibited the proliferation and invasion of RASFs (P<0.001), while inducing their apoptosis (P<0.001). HDAC1 overexpression reversed the biological effects of miR-449 on RASFs (P<0.001). CONCLUSIONS miR-449 inhibits the proliferation and invasion of RASFs and induces their apoptosis by targeting HDAC1, thereby exerting a protective effect against RA.