title: MTDH promotes glioma invasion through regulating miR-130b-ceRNAs.
abstract: Cell invasion is crucial for high mortality and recurrence rate in glioma. Epithelial-mesenchymal transition (EMT) is an important step in cancer invasion. Metadherin (MTDH) contributes to EMT in several cancers, but the role and mechanism of MTDH in EMT-like process of glioma remain unknown. Here we demonstrate that MTDH was overexpressed in glioma tissues and cells and induced EMT-like change and invasion of glioma cells. Interestingly, MTDH could modulate the expression of a group of glioma-related miRNAs. In particular, MTDH upregulated miR-130b transcription via acting as a coactivator of NF-kB. MiR-130b promoted EMT-like change and invasion of glioma cells through targeting multiple EMT-related genes, including PTEN, PPP2CA and SMAD7. In addition, PTEN acted as the competing endogenous RNA (ceRNA) to affect PPP2CA and SMAD7 expression, and inhibited EMT-like change in glioma cells. Furthermore, miR-130b mediated EMT-like change induced by MTDH, and MTDH inhibited the expression levels of PTEN, PPP2CA and SMAD7. Taken together, we reveal a novel mechanism that MTDH induces EMT-like change and invasion of glioma via the regulation of miR-130b-ceRNAs, providing the first direct link between MTDH and miRNAs in cancer cells.
authors.affiliation: Wu Lien-Teh institute, Department of Microbiology, Harbin Medical University, The Heilongjiang Key Laboratory of Immunity and Infection, Pathogen Biology, Harbin 150081, China.
authors.forename: Liping
authors.initials: L
authors.lastname: Tong
authors.affiliation: Department of Neurosurgery, The First Affiliated Hospital, Harbin Medical University, Harbin 150001, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Chu
authors.affiliation: Wu Lien-Teh institute, Department of Microbiology, Harbin Medical University, The Heilongjiang Key Laboratory of Immunity and Infection, Pathogen Biology, Harbin 150081, China.
authors.forename: Bingqing
authors.initials: B
authors.lastname: Yan
authors.affiliation: Department of Neurosurgery, The First Affiliated Hospital, Harbin Medical University, Harbin 150001, China.
authors.forename: Weiyi
authors.initials: W
authors.lastname: Zhao
authors.affiliation: Jiamusi University, Jiamusi 154002, China.
authors.forename: Shuang
authors.initials: S
authors.lastname: Liu
authors.affiliation: Jiamusi University, Jiamusi 154002, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Wei
authors.affiliation: Wu Lien-Teh institute, Department of Microbiology, Harbin Medical University, The Heilongjiang Key Laboratory of Immunity and Infection, Pathogen Biology, Harbin 150081, China.
authors.forename: Huihuang
authors.initials: H
authors.lastname: Lou
authors.affiliation: Department of Neurosurgery, The First Affiliated Hospital, Harbin Medical University, Harbin 150001, China.
authors.forename: Shengkun
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Department of Neurosurgery, The First Affiliated Hospital, Harbin Medical University, Harbin 150001, China.
authors.forename: Shuai
authors.initials: S
authors.lastname: Ma
authors.affiliation: College of Bioinformatics Science and Technology and Bio-Pharmaceutical Key Laboratory of Heilongjiang Province, Harbin Medical University, Harbin 150081, China.
authors.forename: Juan
authors.initials: J
authors.lastname: Xu
authors.affiliation: Wu Lien-Teh institute, Department of Microbiology, Harbin Medical University, The Heilongjiang Key Laboratory of Immunity and Infection, Pathogen Biology, Harbin 150081, China.
authors.forename: Lanlan
authors.initials: L
authors.lastname: Wei
mesh_terms: D015815:Cell Adhesion Molecules / Q000378:metabolism*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D005910:Glioma / Q000235:genetics* / Q000473:pathology*; D057809:HEK293 Cells; D006801:Humans; D008565:Membrane Proteins; D035683:MicroRNAs / Q000096:biosynthesis / Q000235:genetics*; D016328:NF-kappa B / Q000378:metabolism; D009361:Neoplasm Invasiveness / Q000473:pathology; D009364:Neoplasm Recurrence, Local / Q000235:genetics; D051059:PTEN Phosphohydrolase / Q000235:genetics; D054648:Protein Phosphatase 2 / Q000235:genetics; D016601:RNA-Binding Proteins; D015398:Signal Transduction; D051906:Smad7 Protein / Q000235:genetics
chemical_list: D015815:Cell Adhesion Molecules; C554019:MIRN130 microRNA, human; C483039:MTDH protein, human; D008565:Membrane Proteins; D035683:MicroRNAs; D016328:NF-kappa B; D016601:RNA-Binding Proteins; C497806:SMAD7 protein, human; D051906:Smad7 Protein; C517189:PPP2CA protein, human; D054648:Protein Phosphatase 2; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human
keywords: EMT; MTDH; ceRNA; glioma; miR-130b