SAA1 knockdown promotes the apoptosis of glioblastoma cells via downregulation of AKT signaling

Huikai Zhang; Yang Xu; Gang Deng; Fanen Yuan; Yinqiu Tan; Lun Gao; Qian Sun; Yangzhi Qi; Kun Yang; Rongxin Geng; Hongxiang Jiang; Baohui Liu; Qianxue Chen

doi:10.7150/jca.48419

SAA1 knockdown promotes the apoptosis of glioblastoma cells via downregulation of AKT signaling

J Cancer. 2021 Mar 10;12(9):2756-2767. doi: 10.7150/jca.48419. eCollection 2021.

Authors

Huikai Zhang^{1

2}, Yang Xu^{1

2}, Gang Deng^{1

2}, Fanen Yuan^{1

2}, Yinqiu Tan^{1

2}, Lun Gao^{1

2}, Qian Sun^{1

2}, Yangzhi Qi^{1

2}, Kun Yang^{1

2}, Rongxin Geng^{1

2}, Hongxiang Jiang^{1

2}, Baohui Liu^{1

2}, Qianxue Chen^{1

2}

Affiliations

¹ Department of Neurosurgery, Renmin Hospital of Wuhan University, Wuhan, China.
² Central Laboratory, Renmin Hospital of Wuhan University, Wuhan, China.

Abstract

Serum amyloid A1 (SAA1) is an inflammatory associated high-density lipoprotein. And It is also considered as a predictor and prognostic marker of cancer risk. However, its role and mechanisms in glioblastoma (GBM) still unclear. In this study, we validate that SAA1 is up-regulated in GBM, and its high expression predicts poor prognosis. SAA1 knockdown promotes the apoptosis of GBM cell. Mechanistically, SAA1 knockdown can inhibit serine/threonine protein kinase B (AKT) phosphorylation, thereby regulating the expression of apoptosis-related proteins such as Bcl2 and Bax, leading to GBM cell death. Moreover, Gliomas with low SAA1 expression have increased sensitivity to Temozolomide (TMZ). Low SAA1 expression segregated glioma patients who were treated with Temozolomide (TMZ) or with high MGMT promoter methylation into survival groups in TCGA and CGGA dataset. Our study strongly suggested that SAA1 was a regulator of cells apoptosis and acted not only as a prognostic marker but also a novel biomarker of sensitivity of glioma to TMZ.

Keywords: AKT; Apoptosis; Glioblastoma; Serum amyloid A1; Temozolomide..