Repression of Septin9 and Septin2 suppresses tumor growth of human glioblastoma cells

被引:39
作者
Xu, Dongchao [1 ]
Liu, Ajuan [1 ]
Wang, Xuan [1 ]
Chen, Yidan [1 ]
Shen, Yunyun [2 ,3 ]
Tan, Zhou [1 ]
Qiu, Mengsheng [1 ,4 ]
机构
[1] Hangzhou Normal Univ, Coll Life & Environm Sci, Inst Life Sci, Key Lab Organ Dev & Regenerat Zhejiang Prov, Hangzhou 311121, Zhejiang, Peoples R China
[2] Zhejiang Sci Tech Univ, Inst Cognit Neurosci, Hangzhou, Zhejiang, Peoples R China
[3] Zhejiang Sci Tech Univ, Dept Psychol, Hangzhou, Zhejiang, Peoples R China
[4] Univ Louisville, Dept Anat Sci & Neurobiol, Louisville, KY 40292 USA
来源
CELL DEATH & DISEASE | 2018年 / 9卷
基金
中国国家自然科学基金;
关键词
CENTRAL-NERVOUS-SYSTEM; MAMMALIAN SEPTINS; COLORECTAL-CANCER; MALIGNANT GLIOMAS; DNA METHYLATION; DOWN-REGULATION; MULTIFORME; COMBINATION; EXPRESSION; COMPLEXES;
D O I
10.1038/s41419-018-0547-4
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Glioblastoma (GBM) is the most common primary malignancy of the central nervous system (CNS) with <10% 5-year survival rate The growth and invasion of GBM cells into normal brain make the resection and treatment difficult A better understanding of the biology of GBM cells is crucial to the targeted therapies for the disease In this study, we identified Septin9 (SEPT9) and Septin2 (SEPT2) as GBM related genes through integrated multi-omics analysis across independent transcriptomic and proteomic studies Further studies revealed that expression of SEPT9 and SEPT2 was elevated in glioma tissues and cell lines (A172, U87 MG) Knockdown of SEPT9 and SEPT2 in A172/U87 MG was able to inhibit GBM cell proliferation and arrest cell cycle progression in the S phase in a synergistic mechanism Moreover, suppression of SEPT9 and SEPT2 decreased the GBM cell invasive capability and significantly impaired the growth of glioma xenografts in nude mice Furthermore, the decrease in GBM cell growth caused by SEPT9 and SEPT2 RNAi appears to involve two parallel signaling pathway including the p53/p21 axis and MEK/ERK activation Together, our integration of multi-omics analysis has revealed previously unrecognized synergistic role of SEPT9 and SEPT2 in GBM, and provided novel insights into the targeted therapy of GBM
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页数:13
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