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MAGI3通过上调PTEN表达抑制胶质瘤细胞增殖。

MAGI3 Suppresses Glioma Cell Proliferation via Upregulation of PTEN Expression.

作者信息

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

机构信息

Department of Biochemistry and Molecular Biology, Capital Medical University, Beijing 100069, China; The Center of Prenatal Diagnosis, First Affiliated Hospital, College of Medicine, Zhengzhou University, Zhengzhou 450052, Henan, China.

Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing 100050, China; China National Clinical Research Center for Neurological Diseases, Beijing 100050, China.

出版信息

Biomed Environ Sci. 2015 Jul;28(7):502-9. doi: 10.3967/bes2015.072.

DOI:10.3967/bes2015.072

PMID:26248734

Abstract

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 glioma may enhance the proliferation of glioma cells via downregulation of PTEN expression, leading to the activation of the PI3K/Akt pathway. MAGI3 is a potential glioma suppressor.

摘要

目的

探讨膜相关鸟苷酸激酶倒转3（MAGI3）在胶质瘤细胞增殖中的作用及分子机制。

方法

采用蛋白质免疫印迹法检测胶质瘤样本中MAGI3和PTEN的表达水平。将MAGI3稳定转染至C6胶质瘤细胞中，获得C6-MAGI3细胞。然后，评估C6和C6-MAGI3细胞的增殖情况、MAGI3和PTEN的表达水平以及Akt磷酸化水平。通过将C6和C6-MAGI3细胞皮下注射到裸鼠体内建立异种移植肿瘤模型，并比较小鼠体内异种移植瘤的生长速率。使用基因集富集分析（GSEA），通过检测胶质瘤数据集中MAGI3表达与PI3K/Akt信号下游靶基因表达之间的相关性，进一步研究MAGI3表达在PI3K/Akt信号激活中的潜在作用。

结果

胶质瘤中MAGI3和PTEN的表达水平显著下调。在胶质瘤C6细胞系中过表达MAGI3可上调PTEN蛋白表达，抑制Akt磷酸化，并抑制细胞增殖。MAGI3过表达还可抑制裸鼠体内C6胶质瘤异种移植瘤的生长。基于GEO数据库的分析证实，人类胶质瘤样本中PI3K/Akt通路激活与MAGI3 mRNA水平呈负相关。