title: Downregulation of TLX induces TET3 expression and inhibits glioblastoma stem cell self-renewal and tumorigenesis.
abstract: Glioblastomas have been proposed to be maintained by highly tumorigenic glioblastoma stem cells (GSCs) that are resistant to current therapy. Therefore, targeting GSCs is critical for developing effective therapies for glioblastoma. In this study, we identify the regulatory cascade of the nuclear receptor TLX and the DNA hydroxylase Ten eleven translocation 3 (TET3) as a target for human GSCs. We show that knockdown of TLX expression inhibits human GSC tumorigenicity in mice. Treatment of human GSC-grafted mice with viral vector-delivered TLX shRNA or nanovector-delivered TLX siRNA inhibits tumour development and prolongs survival. Moreover, we identify TET3 as a potent tumour suppressor downstream of TLX to regulate the growth and self-renewal in GSCs. This study identifies the TLX-TET3 axis as a potential therapeutic target for glioblastoma.
authors.affiliation: Department of Developmental and Stem Cell Biology, Division of Stem Cell Biology Research, Cancer Center, Beckman Research Institute of City of Hope, 1500 E. Duarte Road, Duarte, California 91010, USA.|Irell and Manella Graduate School of Biological Sciences, Beckman Research Institute of City of Hope, 1500 E. Duarte Road, Duarte, California 91010, USA.
authors.forename: Qi
authors.initials: Q
authors.lastname: Cui
authors.affiliation: Department of Developmental and Stem Cell Biology, Division of Stem Cell Biology Research, Cancer Center, Beckman Research Institute of City of Hope, 1500 E. Duarte Road, Duarte, California 91010, USA.|Irell and Manella Graduate School of Biological Sciences, Beckman Research Institute of City of Hope, 1500 E. Duarte Road, Duarte, California 91010, USA.
authors.forename: Su
authors.initials: S
authors.lastname: Yang
authors.affiliation: Department of Developmental and Stem Cell Biology, Division of Stem Cell Biology Research, Cancer Center, Beckman Research Institute of City of Hope, 1500 E. Duarte Road, Duarte, California 91010, USA.
authors.forename: Peng
authors.initials: P
authors.lastname: Ye
authors.affiliation: Department of Developmental and Stem Cell Biology, Division of Stem Cell Biology Research, Cancer Center, Beckman Research Institute of City of Hope, 1500 E. Duarte Road, Duarte, California 91010, USA.
authors.forename: E
authors.initials: E
authors.lastname: Tian
authors.affiliation: Department of Developmental and Stem Cell Biology, Division of Stem Cell Biology Research, Cancer Center, Beckman Research Institute of City of Hope, 1500 E. Duarte Road, Duarte, California 91010, USA.
authors.forename: Guoqiang
authors.initials: G
authors.lastname: Sun
authors.affiliation: Department of Molecular and Cellular Biology, Beckman Research Institute of City of Hope, 1500 E. Duarte Road, Duarte, California 91010, USA.
authors.forename: Jiehua
authors.initials: J
authors.lastname: Zhou
authors.affiliation: Department of Diabetes and Metabolic Diseases Research, Beckman Research Institute of City of Hope, 1500 E. Duarte Road, Duarte, California 91010, USA.
authors.forename: Guihua
authors.initials: G
authors.lastname: Sun
authors.affiliation: Aix-Marseille Université, CNRS, UMR 7325, Centre Interdisciplinaire de Nanoscience de Marseille, 13288 Marseille, France.
authors.forename: Xiaoxuan
authors.initials: X
authors.lastname: Liu
authors.affiliation: Aix-Marseille Université, CNRS, UMR 7325, Centre Interdisciplinaire de Nanoscience de Marseille, 13288 Marseille, France.
authors.forename: Chao
authors.initials: C
authors.lastname: Chen
authors.affiliation: Department of Developmental and Stem Cell Biology, Division of Stem Cell Biology Research, Cancer Center, Beckman Research Institute of City of Hope, 1500 E. Duarte Road, Duarte, California 91010, USA.
authors.forename: Kiyohito
authors.initials: K
authors.lastname: Murai
authors.affiliation: Department of Developmental and Stem Cell Biology, Division of Stem Cell Biology Research, Cancer Center, Beckman Research Institute of City of Hope, 1500 E. Duarte Road, Duarte, California 91010, USA.
authors.forename: Chunnian
authors.initials: C
authors.lastname: Zhao
authors.affiliation: Department of Molecular and Cellular Biology, Beckman Research Institute of City of Hope, 1500 E. Duarte Road, Duarte, California 91010, USA.
authors.forename: Krist T
authors.initials: KT
authors.lastname: Azizian
authors.affiliation: Integrative Genomics Core, Beckman Research Institute of City of Hope, 1500 E. Duarte Road, Duarte, California 91010, USA.
authors.forename: Lu
authors.initials: L
authors.lastname: Yang
authors.affiliation: Integrative Genomics Core, Beckman Research Institute of City of Hope, 1500 E. Duarte Road, Duarte, California 91010, USA.
authors.forename: Charles
authors.initials: C
authors.lastname: Warden
authors.affiliation: Integrative Genomics Core, Beckman Research Institute of City of Hope, 1500 E. Duarte Road, Duarte, California 91010, USA.
authors.forename: Xiwei
authors.initials: X
authors.lastname: Wu
authors.affiliation: Department of Pathology, Beckman Research Institute of City of Hope, 1500 E. Duarte Road, Duarte, California 91010, USA.
authors.forename: Massimo
authors.initials: M
authors.lastname: D'Apuzzo
authors.affiliation: Department of Hematology and Hematopoietic Cell Transplantation, Beckman Research Institute of City of Hope, 1500 E. Duarte Road, Duarte, California 91010, USA.
authors.forename: Christine
authors.initials: C
authors.lastname: Brown
authors.affiliation: Department of Surgery, Beckman Research Institute of City of Hope, 1500 E. Duarte Road, Duarte, California 91010, USA.
authors.forename: Behnam
authors.initials: B
authors.lastname: Badie
authors.affiliation: Aix-Marseille Université, CNRS, UMR 7325, Centre Interdisciplinaire de Nanoscience de Marseille, 13288 Marseille, France.
authors.forename: Ling
authors.initials: L
authors.lastname: Peng
authors.affiliation: Department of Diabetes and Metabolic Diseases Research, Beckman Research Institute of City of Hope, 1500 E. Duarte Road, Duarte, California 91010, USA.
authors.forename: Arthur D
authors.initials: AD
authors.lastname: Riggs
authors.affiliation: Irell and Manella Graduate School of Biological Sciences, Beckman Research Institute of City of Hope, 1500 E. Duarte Road, Duarte, California 91010, USA.|Department of Molecular and Cellular Biology, Beckman Research Institute of City of Hope, 1500 E. Duarte Road, Duarte, California 91010, USA.
authors.forename: John J
authors.initials: JJ
authors.lastname: Rossi
authors.affiliation: Department of Developmental and Stem Cell Biology, Division of Stem Cell Biology Research, Cancer Center, Beckman Research Institute of City of Hope, 1500 E. Duarte Road, Duarte, California 91010, USA.|Irell and Manella Graduate School of Biological Sciences, Beckman Research Institute of City of Hope, 1500 E. Duarte Road, Duarte, California 91010, USA.
authors.forename: Yanhong
authors.initials: Y
authors.lastname: Shi
mesh_terms: D000818:Animals; D001932:Brain Neoplasms / Q000235:genetics*; D063646:Carcinogenesis / Q000235:genetics*; D000066673:Cell Self Renewal / Q000235:genetics*; D047369:Chromatin Immunoprecipitation; D049308:Dioxygenases / Q000235:genetics*; D015536:Down-Regulation; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D005909:Glioblastoma / Q000235:genetics*; D006801:Humans; D051379:Mice; D009368:Neoplasm Transplantation; D014411:Neoplastic Stem Cells / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D057093:Orphan Nuclear Receptors; D060888:Real-Time Polymerase Chain Reaction; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics*; D014410:Tumor Stem Cell Assay
chemical_list: C088601:NR2E1 protein, human; D057093:Orphan Nuclear Receptors; D018160:Receptors, Cytoplasmic and Nuclear; C578792:TET3 protein, human; D049308:Dioxygenases
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