MicroRNA-34a Promotes Apoptosis of Rheumatoid Arthritis Fbroblast-Like Synoviocyte via AMPK/Akt/mTOR Signaling Pathway

Abstract

Background and Objectives: Rheumatoid arthritis (RA) is an autoimmune arthropathy characterised by chronic synovitis, joint cartilage breakdown and bone erosions. The life quality of RA patients has been substantially effected by the disease and it is of great significance to search for more efficacious and novel therapeutic agents. Methods: In this study, mRNA levels of miR-34a in HFLS and RA-FLS were examined by RT-PCR. CCK8 assay was applied to detect the viability of RA-FLS transfected with miR-34a mimic or inhibitor. Furthermore, TUNEL assay and Hoechest-33342 assay was applied to detect the apoptosis of RA-FLS transfected with miR-34a mimic or inhibitor. The expressions of proteins related to AMPK/Akt/mTOR and autophagy were also detected by western blot. Results: The RT-PCR result showed that miR-34a mRNA levels was markedly downregulated in RA-FLS compared to HFLS. CCK8 assay results demonstrated that miR-34a overexpression significantly suppressed RA-FLS proliferation and miR-34a interference had the opposite effect. TUNEL assay and Hoechest-33342 assay demonstrated that miR-34a overexpression significantly promoted RA-FLS apoptosis and miR-34a interference had the opposite effect. The western blot results revealed that miR-34a can affect autophagy via AMPK/Akt/mTOR signaling pathway. Conclusion: This study suggested that miR-34a can regulate proliferation and apoptosis in RA-FLS by affecting autophagy through AMPK/Akt/mTOR signaling pathway.