title: MAGI3 Suppresses Glioma Cell Proliferation via Upregulation of PTEN Expression.
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.
  
  
  CONCLUSIONS
  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.affiliation: 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.
authors.forename: Qian
authors.initials: Q
authors.lastname: Ma
authors.affiliation: Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing 100050, China; China National Clinical Research Center for Neurological Diseases, Beijing 100050, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Biochemistry and Molecular Biology, Capital Medical University, Beijing 100069, China.
authors.forename: Ran
authors.initials: R
authors.lastname: Meng
authors.affiliation: Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing 100050, China; China National Clinical Research Center for Neurological Diseases, Beijing 100050, China.
authors.forename: Kun Ming
authors.initials: KM
authors.lastname: Xie
authors.affiliation: Department of Biochemistry and Molecular Biology, Capital Medical University, Beijing 100069, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Xiong
authors.affiliation: Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing 100050, China; China National Clinical Research Center for Neurological Diseases, Beijing 100050, China.
authors.forename: Song
authors.initials: S
authors.lastname: Lin
authors.affiliation: UC Berkeley, San Francisco, Cao 94720-5800, USA.
authors.forename: Zong Lin K
authors.initials: ZL
authors.lastname: He
authors.affiliation: Department of Biochemistry and Molecular Biology, Capital Medical University, Beijing 100069, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Tao
authors.affiliation: Core Facilities Center, Capital Medical University, Beijing 100069, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing 100050, China; China National Clinical Research Center for Neurological Diseases, Beijing 100050, China.
authors.forename: Ji Zong
authors.initials: JZ
authors.lastname: Zhao
authors.affiliation: Department of Biochemistry and Molecular Biology, Capital Medical University, Beijing 100069, China.
authors.forename: Jun Qi
authors.initials: JQ
authors.lastname: He
mesh_terms: D000818:Animals; D001932:Brain Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics; D015536:Down-Regulation; D005910:Glioma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D008819:Mice, Nude; D051059:PTEN Phosphohydrolase / Q000235:genetics* / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051381:Rats; D015398:Signal Transduction; D014162:Transfection; D015854:Up-Regulation; D023041:Xenograft Model Antitumor Assays
chemical_list: C496469:MAGI3 protein, human; D008565:Membrane Proteins; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human
keywords: Glioma; MAGI3; PDZ; PI3K/Akt; PTEN; Protein-protein interaction