title: MAGI3 negatively regulates Wnt/β-catenin signaling and suppresses malignant phenotypes of glioma cells.
abstract: Gliomas are the most common primary brain malignancies and are associated with a poor prognosis. Here, we showed that the PDZ domain-containing protein membrane-associated guanylate kinase inverted 3 (MAGI3) was downregulated at the both mRNA and protein levels in human glioma samples. MAGI3 inhibited proliferation, migration, and cell cycle progression of glioma cells in its overexpression and knockdown studies. By using GST pull-down and co-immunoprecipitation assays, we found that MAGI3 bound to β-catenin through its PDZ domains and the PDZ-binding motif of β-catenin. MAGI3 overexpression inhibited β-catenin transcriptional activity via its interaction with β-catenin. Consistently, MAGI3 overexpression in glioma cells C6 suppressed expression of β-catenin target genes including Cyclin D1 and Axin2, whereas MAGI3 knockdown in glioma cells U373 and LN229 enhanced their expression. MAGI3 overexpression decreased growth of C6 subcutaneous tumors in mice, and inhibited expression of β-catenin target genes in xenograft tumors. Furthermore, analysis based on the Gene Expression Omnibus (GEO) glioma dataset showed association of MAGI3 expression with overall survival and tumor grade. Finally, we demonstrated negative correlation between MAGI3 expression and activity of Wnt/β-catenin signaling through GSEA of three public glioma datasets and immunohistochemical staining of clinical glioma samples. Taken together, these results identify MAGI3 as a novel tumor suppressor and provide insight into the pathogenesis of glioma.
authors.affiliation: Department of Biochemistry and Molecular Biology, Capital Medical University, Beijing 100069, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Ma
authors.affiliation: Core Facilities Center, Capital Medical University, Beijing 100069, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Department of Interventional Radiology, First Hospital of Shanxi Medical University, Taiyuan 030001, China.
authors.forename: Duiping
authors.initials: D
authors.lastname: Feng
authors.affiliation: Department of Biochemistry and Molecular Biology, Capital Medical University, Beijing 100069, China.
authors.forename: Shuai
authors.initials: S
authors.lastname: Zheng
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 Biochemistry and Molecular Biology, Capital Medical University, Beijing 100069, China.
authors.forename: Pengyan
authors.initials: P
authors.lastname: Fa
authors.affiliation: Department of Biochemistry and Molecular Biology, Capital Medical University, Beijing 100069, China.
authors.forename: Chunjuan
authors.initials: C
authors.lastname: Zhao
authors.affiliation: Department of Biochemistry and Molecular Biology, Capital Medical University, Beijing 100069, China.
authors.forename: Hua
authors.initials: H
authors.lastname: Liu
authors.affiliation: Department of Biochemistry and Molecular Biology, Capital Medical University, Beijing 100069, China.
authors.forename: Ran
authors.initials: R
authors.lastname: Song
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: Department of Biochemistry and Molecular Biology, Capital Medical University, Beijing 100069, China.
authors.forename: Longyan
authors.initials: L
authors.lastname: Yang
authors.affiliation: Department of Pathology, Capital Medical University, Beijing 100069, China.|Beijing Key Laboratory for Tumor Invasion and Metastasis, Capital Medical University-Cardiff University Joint Centre for Biomedical Research, Cancer Institute of Capital Medical University, Beijing 100069, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Dai
authors.affiliation: Department of Biochemistry and Molecular Biology, Capital Medical University, Beijing 100069, China.|Molecular Laboratory for Gene Therapy and Tooth Regeneration, Capital Medical University School of Stomatology, Beijing 100050, China.
authors.forename: Songlin
authors.initials: S
authors.lastname: Wang
authors.affiliation: Beijing Key Laboratory for Tumor Invasion and Metastasis, Capital Medical University-Cardiff University Joint Centre for Biomedical Research, Cancer Institute of Capital Medical University, Beijing 100069, China.|Metastasis and Angiogenesis Research Group, Department of Surgery, Cardiff University School of Medicine, Heath Park, Cardiff, CF14 4XN, U.K.
authors.forename: Wen G
authors.initials: WG
authors.lastname: Jiang
authors.affiliation: Department of Biochemistry and Molecular Biology, Capital Medical University, Beijing 100069, China.|Beijing Key Laboratory for Tumor Invasion and Metastasis, Capital Medical University-Cardiff University Joint Centre for Biomedical Research, Cancer Institute of Capital Medical University, Beijing 100069, China.
authors.forename: Junqi
authors.initials: J
authors.lastname: He
mesh_terms: D000818:Animals; D001932:Brain Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D019556:COS Cells; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000502:physiology; D005910:Glioma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D057809:HEK293 Cells; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D010641:Phenotype; D010766:Phosphorylation; D051381:Rats; D014162:Transfection; D060449:Wnt Signaling Pathway
chemical_list: C496469:MAGI3 protein, human; D008565:Membrane Proteins
keywords: MAGI3; PDZ; glioma; protein-protein interaction; β-catenin