NFAT1-regulated IL6 signalling contributes to aggressive phenotypes of glioma

Cell Communication and Signaling

Research

Sheng Han¹  Anhua Wu¹  Yang Jiang¹  Zixun Wang¹  Wen Cheng¹ 

[1] Department of Neurosurgery, The First Hospital of China Medical University, Nanjing Street 155, Heping District, 110001, Shenyang, China;

关键词: Glioma;    Glioblastoma;    IL6;    IL6R;    NFAT1;   

DOI  :  10.1186/s12964-017-0210-1

 received in 2017-10-05, accepted in 2017-12-12,  发布年份 2017

来源: Springer

【 摘 要 】

BackgroundWe previously demonstrated that the local immune status correlated with the glioma prognosis. Interleukin-6 (IL6) was identified as an important local immune-related risk marker related to unfavourable prognosis. In this study, we further investigated the role and regulation of IL6 signalling in glioma.MethodsThe expression and prognostic value of IL6 and the IL6 receptor (IL6R) were explored in The Cancer Genome Atlas (TCGA) and REMBRANDT databases and clinical samples. Functional effects of genetic knockdown and overexpression of IL6R or IL6 stimulation were examined in vitro and in tumours in vivo. The effects of the nuclear factor of activated T cells-1 (NFAT1) on the promoter activities of IL6R and IL6 were also examined.ResultsHigh IL6- and IL6R-expression were significantly associated with mesenchymal subtype and IDH-wildtype gliomas, and were predictors of poor survival. Knockdown of IL6R decreased cell proliferation, invasion and neurosphere formation in vitro, and inhibited tumorigenesis in vivo. IL6R overexpression or IL6 stimulation enhanced the invasion and growth of glioma cells. TCGA database searching revealed that IL6- and IL6R-expression were correlated with that of NFAT1. In glioma cells, NFAT1 enhanced the promoter activities of IL6R and IL6, and upregulated the expression of both IL6R and IL6.ConclusionNFAT1-regulated IL6 signalling contributes to aggressive phenotypes of gliomas, emphasizing the role of immunomodulatory factors in glioma malignant progression.

【 授权许可】

CC BY   
© The Author(s). 2017