title: MicroRNA-155 promotes glioma cell proliferation via the regulation of MXI1.
abstract: Gliomas are the most common and aggressive primary tumors in the central nervous system. Recently, Max interactor-1 (MXI1), an antagonist of c-Myc that is involved in brain tumor progression, has been reported to be deregulated in a variety of tumors including glioma. However, the mechanism of MXI1 deregulation in gliomas remains unclear. In this study, we show that the relative expression level of MXI1 is markedly down-regulated in glioma cell lines. Using integrated bioinformatic analysis and experimental confirmation, we identified several miRNAs by screening a panel of predicted miRNAs that may regulate the MXI1 3'UTR. The strongest inhibitory miRNA, miR-155, can attenuate the activity of a luciferase reporter gene that is fused with the MXI1 3'UTR and decrease the expression levels of MXI1 mRNA and protein in U87 glioma cells. The potential role of miR-155 in promoting glioma cell proliferation by targeting MXI1 was confirmed in various glioma cell lines by rescue experiments using MTT assays, EdU incorporation assay, and cell counting experiments. In addition, we determined that the level of MXI1 mRNA was inversely correlated with the expression of miR-155 in 18 sets of glioblastoma multiforme specimens. These findings reveal for the first time that the targeting of MXI1 by miR-155 may result in a reduction in MXI1 expression and promote glioma cell proliferation; this result suggests a novel function of miR-155 in targeting MXI1 in glioma-genesis.
authors.affiliation: State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou, China ; Key Laboratory of Gene Engineering of the Ministry of Education, School of Life Sciences, Sun Yat-sen University, Guangzhou, China ; Department of Pathology, First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
authors.forename: Jianwen
authors.initials: J
authors.lastname: Zhou
authors.affiliation: Neurosurgery Department, Epilepsy Centre, Guangzhou General Hospital, Guangzhou Command, PLA, Guangzhou, China ; HuaBo Bio-Pharmaceutic Institute of Guangzhou, Guangzhou, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.affiliation: Department of Radiology, First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
authors.forename: Zhenhua
authors.initials: Z
authors.lastname: Gao
authors.affiliation: State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou, China ; Shenzhen State High-Tech Industrial Innovation Centre, Shenzhen, China.
authors.forename: Xueling
authors.initials: X
authors.lastname: Peng
authors.affiliation: Key Laboratory of Gene Engineering of the Ministry of Education, School of Life Sciences, Sun Yat-sen University, Guangzhou, China.
authors.forename: Xulin
authors.initials: X
authors.lastname: Chen
authors.affiliation: Department of Gynecology, the Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou, China.
authors.forename: Weiyi
authors.initials: W
authors.lastname: Xu
authors.affiliation: Department of Neurosurgery, Affiliated Shantou Hospital of Sun Yat-sen University, Shantou, China.
authors.forename: Haixiong
authors.initials: H
authors.lastname: Xu
authors.affiliation: Biomedical Eng. Res. Center, Kunming Medical University, Kunming, China.
authors.forename: Marie C
authors.initials: MC
authors.lastname: Lin
authors.affiliation: State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou, China ; Key Laboratory of Gene Engineering of the Ministry of Education, School of Life Sciences, Sun Yat-sen University, Guangzhou, China.
authors.forename: Songshan
authors.initials: S
authors.lastname: Jiang
mesh_terms: D020413:3' Untranslated Regions; D001483:Base Sequence; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics* / Q000378:metabolism; D001932:Brain Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D044127:Epigenesis, Genetic; D015972:Gene Expression Regulation, Neoplastic; D017930:Genes, Reporter; D005909:Glioblastoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D008969:Molecular Sequence Data; D025521:Tumor Suppressor Proteins / Q000235:genetics* / Q000378:metabolism
chemical_list: D020413:3' Untranslated Regions; D051792:Basic Helix-Loop-Helix Proteins; D008156:Luciferases; D035683:MicroRNAs; D025521:Tumor Suppressor Proteins; C524942:MIRN155 microRNA, human; C079440:MXI1 protein, human