Rheumatoid Arthritis Fibroblast-like Synoviocyte Suppression Mediated by PTEN Involves Survivin Gene Silencing

Abstract

Abstract Survivin is a proto-oncogene biomarker known for its anti-apoptotic and cell cycle regulating properties induced by the activation of the phosphoinositide 3-kinase (PI3K)/Akt pathway. In the context of non-cancer pathology, such as rheumatoid arthritis (RA), survivin has emerged as a feature associated with severe joint damage and poor treatment response. Phosphatase and tensin homolog (PTEN) is a phosphatase antagonizing all classes of PI3K. The interplay between survivin oncogenic mechanisms and proliferation suppression networks in RA has remained largely elusive. This study investigated the effect of PTEN on survivin gene expression in rheumatiod arthritis fibroblast-like synoviocyte (RA-FLS). We showed for the first time that the suppression of RA-FLS was mediated by PTEN involving survivin silencing. Considering that survivin suppressants are currently available in clinical trials and clinical use, their effects in RA-FLS support a probably RA therapy to clinical practice.