Qian Ma1, Yan Zhang2, Ran Meng3, Kun Ming Xie2, Ying Xiong3, Song Lin2, Zong Lin K He4, Tao Tao3, Ying Yang5, Ji Zong Zhao2, Jun Qi He3. 1. 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. 2. Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing 100050, China; China National Clinical Research Center for Neurological Diseases, Beijing 100050, China. 3. Department of Biochemistry and Molecular Biology, Capital Medical University, Beijing 100069, China. 4. UC Berkeley, San Francisco, Cao 94720-5800, USA. 5. Core Facilities Center, Capital Medical University, Beijing 100069, China.
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.
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 humanglioma 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.
Authors: Juncheng Dai; Zhihua Li; Christopher I Amos; Rayjean J Hung; Adonina Tardon; Angeline S Andrew; Chu Chen; David C Christiani; Demetrios Albanes; Erik H F M van der Heijden; Eric J Duell; Gad Rennert; James D Mckay; Jian-Min Yuan; John K Field; Jonas Manjer; Kjell Grankvist; Loic Le Marchand; M Dawn Teare; Matthew B Schabath; Melinda C Aldrich; Ming-Sound Tsao; Philip Lazarus; Stephen Lam; Stig E Bojesen; Susanne Arnold; Xifeng Wu; Aage Haugen; Vladimir Janout; Mikael Johansson; Yonathan Brhane; Ana Fernandez-Somoano; Lambertus A Kiemeney; Michael P A Davies; Shanbeh Zienolddiny; Zhibin Hu; Hongbing Shen Journal: Carcinogenesis Date: 2019-05-14 Impact factor: 4.944