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

Danna Chen,Jianhua Xu,Anping Peng,Fudong Luo,Lin Chen,Jiarui Xu,Li Lin,Dan Liu,Xianzhang Huang,Min He,Dongdong Liu,Junhua Zhuang

doi:10.1038/s41598-017-00517-w

Danna Chen, Jianhua Xu + Show 10 more

Open Access

PDF Available

https://doi.org/10.1038/s41598-017-00517-w

Copy DOI

Export

Save

Cite

Abstract
Highlights/Summary
Full-Text PDF
Similar Papers

Abstract

Listen

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.

Highlights

Survivin is the smallest member of the inhibitor of apoptosis protein (IAP) family and it is encoded by the BIRC5 gene[2]
Recent reports showed that survivin is a direct target gene of the phosphatidylinositol 3-kinase (PI3K)/AKT signaling pathway in the ectopic endometrium and invasive epithelium cells in adenomyosis[16,17,18]
This study shows a close relationship between Phosphatase and tensin homolog (PTEN) and survivin for most rheumatoid arthritis (RA)-FLS functional processes that induce the pathogenesis of RA, such as cell proliferation, migration, invasion and inflammation

Summary

Introduction

Survivin is the smallest member of the inhibitor of apoptosis protein (IAP) family and it is encoded by the BIRC5 gene[2]. It has recently emerged as a biomarker of RA. Studies suggest that the PI3K/ PTEN axis controls multiple aspects in the pathogenesis of inflammatory diseases such as cell migration, invasive behavior, cytokine production and proliferation, and T cell polarization[12,13,14,15]. Recent reports showed that survivin is a direct target gene of the PI3K/AKT signaling pathway in the ectopic endometrium and invasive epithelium cells in adenomyosis[16,17,18]. We determined whether PTEN effects survivin gene expression in rheumatiod arthritis fibroblast-like synoviocyte (RA-FLS)

Methods

Results

Conclusion