MAGI3 Suppresses Glioma Cell Proliferation via Upregulation of PTEN Expression

作     者：MA Qian ZHANG Yan MENG Ran XIE Kun Ming XIONG Ying LIN Song HE Zong Lin K. TAO Tao YANG Ying ZHAO Ji Zong HE Jun Qi 

作者机构：Department of Biochemistry and Molecular Biology Capital Medical University The Center of Prenatal DiagnosisFirst Affiliated HospitalCollege of MedicineZhengzhou Universit Department of Neurosurgery Beijing Tiantan Hospital Capital Medical University China National Clinical Research Center for Neurological Diseases UC BerkeleySan Francisco Core Facilities Center Capital Medical University 

出 版 物：《Biomedical and Environmental Sciences》 (生物医学与环境科学（英文版）)

年 卷 期：2015年第28卷第7期

页      面：502-509页

核心收录：

学科分类：1002[医学-临床医学] 100214[医学-肿瘤学] 10[医学] 

基　　金：supported by the National Natural Science Foundation of the People’s Republic of China(No.81272887 and 81141033) Beijing Municipal Natural Science Foundation(No.7131003) 

主　　题：Glioma PTEN MAGI3 PDZ Protein-protein interaction PI3K/Akt 

摘      要：Objective To investigate the role and molecular mechanism of membrane-associated guanylate kinase inverted 3 （MAGI3） in glioma cell proliferation. Methods The expression levels of MAGI3 and PTEN were assessed in glioma samples by Western blotting. MAGI3 was stably transfected into C6 glioma cells to obtain C6-MAGI3 cells. Then, the proliferation, the expression levels of MAGI3 and PTEN, and Akt phosphorylation were evaluated in C6 and C6-MAGI3 cells. Xenograft tumor models were established by subcutaneous injection of C6 and C6-MAGI3 cells into nude mice, and the growth rates of xenografts in the mice were compared. The potential role of MAGI3 expression in PI3K/Akt signaling activation was further investigated by examining the correlation between MAGI3 expression and the expression of PI3K/Akt signaling downstream target genes in a glioma dataset using gene set enrichment analysis （GSEA）. Results Expression levels of MAGI3 and PTEN were significantly downregulated in gliomas. Overexpression of MAGI3 in the glioma C6 cell line upregulated PTEN protein expression, inhibited the phosphorylation of Akt, and suppressed cell proliferation. MAGI3 overexpression also inhibited the growth of C6 glioma tumor xenografts in nude mice. Analysis based on the GEO database confirmed the negative correlation between activation of PI3K/Akt pathway and MAGI3 mRNA levels in human glioma samples. Conclusion The loss of MAGI3 expression in downregulation of PTEN expression, leading potential glioma suppressor. glioma may enhance the proliferation of glioma cells via to the activation of the PI3K/Akt pathway. MAGI3 is a