Hypomethylation-driven AKT Serine/Threonine Kinase 3 promotes testicular germ cell tumors proliferation and negatively correlates to immune infiltration

Bioengineered

Yang Luo¹  Xingming Wang²  Hao Bo³  Liqing Fan³  Fang Zhu³  Qianyin Zhou³ 

[1] Center for Reproductive Medicine, Key Laboratory for Major Obstetric Diseases of Guangdong Province, the Third Affiliated Hospital of Guangzhou Medical University;Central South University;School of Basic Medical Science, Central South University;

关键词: tgct;    akt3;    methylation;    proliferation;    immunity;   

DOI  :  10.1080/21655979.2021.2002621

来源: DOAJ

【 摘 要 】

AKT Serine/Threonine Kinase 3 (AKT3) has been reported to play an important role in different tumors. However, its clinical value, biological function, and molecular mechanism in testicular germ cell tumors (TGCT) remains unclear. In the current study, we applied the Gene Set Cancer Analysis (GSCA), UCSC XENA, Gene Expression Omnibus (GEO), the Human Protein Atlas (HPA), LinkedOmics, DiseaseMeth version 2.0, TISIDB, and other databases for TGCT data mining. Then, we investigated AKT3’s mechanism of action and clinical survival significance via bioinformatics followed by in vitro experiments. We found that AKT3 was upregulated and had frequent copy number amplifications in TGCT, which were associated with poor survival outcomes of patients. On the other hand, mutations that led to AKT3 loss-of-function were correlated to a better prognosis in patients. Moreover, AKT3 silencing significantly inhibited the proliferation, DNA synthesis and colony formation of NCCIT cells (a TGCT cell line). AKT3 might participate in TGCT progression through multiple signaling pathways, such as ErbB, oxidative phosphorylation, and affecting tumor immune infiltration. Also, the upregulation of AKT3 mRNA expression might be driven by the hypomethylation of its promoter region. Overall, AKT3 is a potential TGCT oncogene and can be further used as a therapeutic target.

【 授权许可】

Unknown