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miR-182 integrates apoptosis, growth, and differentiation programs in glioblastoma.
Kouri, Fotini M; Hurley, Lisa A; Daniel, Weston L; Day, Emily S; Hua, Youjia; Hao, Liangliang; Peng, Chian-Yu; Merkel, Timothy J; Queisser, Markus A; Ritner, Carissa; Zhang, Hailei; James, C David; Sznajder, Jacob I; Chin, Lynda; Giljohann, David A; Kessler, John A; Peter, Marcus E; Mirkin, Chad A; Stegh, Alexander H.
Afiliação
  • Kouri FM; Ken and Ruth Davee Department of Neurology, Feinberg School of Medicine, Chicago, Illinois 60611, USA; The Brain Tumor Institute, The Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, Illinois 60611, USA;
  • Hurley LA; Ken and Ruth Davee Department of Neurology, Feinberg School of Medicine, Chicago, Illinois 60611, USA; The Brain Tumor Institute, The Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, Illinois 60611, USA;
  • Daniel WL; AuraSense Therapeutics, Skokie, Illinois 60077, USA;
  • Day ES; Department of Chemistry, Northwestern University, Evanston, Illinois 60208, USA; International Institute for Nanotechnology, Northwestern University, Evanston, Illinois 60208, USA;
  • Hua Y; Division Hematology/Oncology, Feinberg School of Medicine, Chicago, Illinois 60611, USA; The Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, Illinois 60611, USA;
  • Hao L; Department of Chemistry, Northwestern University, Evanston, Illinois 60208, USA; International Institute for Nanotechnology, Northwestern University, Evanston, Illinois 60208, USA;
  • Peng CY; Ken and Ruth Davee Department of Neurology, Feinberg School of Medicine, Chicago, Illinois 60611, USA; The Brain Tumor Institute, The Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, Illinois 60611, USA;
  • Merkel TJ; Department of Chemistry, Northwestern University, Evanston, Illinois 60208, USA; International Institute for Nanotechnology, Northwestern University, Evanston, Illinois 60208, USA;
  • Queisser MA; Division of Pulmonary and Critical Care Medicine, Northwestern University, Chicago, Illinois 60611, USA;
  • Ritner C; Ken and Ruth Davee Department of Neurology, Feinberg School of Medicine, Chicago, Illinois 60611, USA; The Brain Tumor Institute, The Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, Illinois 60611, USA;
  • Zhang H; The Broad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, Massachusetts 02142, USA; Harvard Medical School, Boston, Massachusetts 02115, USA; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts 02115, USA; Department of Genomic Medicine, The
  • James CD; Department of Neurological Surgery, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, 60611, USA.
  • Sznajder JI; Division of Pulmonary and Critical Care Medicine, Northwestern University, Chicago, Illinois 60611, USA;
  • Chin L; The Broad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, Massachusetts 02142, USA; Harvard Medical School, Boston, Massachusetts 02115, USA; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts 02115, USA; Department of Genomic Medicine, The
  • Giljohann DA; AuraSense Therapeutics, Skokie, Illinois 60077, USA;
  • Kessler JA; Ken and Ruth Davee Department of Neurology, Feinberg School of Medicine, Chicago, Illinois 60611, USA; The Brain Tumor Institute, The Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, Illinois 60611, USA;
  • Peter ME; Division Hematology/Oncology, Feinberg School of Medicine, Chicago, Illinois 60611, USA; The Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, Illinois 60611, USA;
  • Mirkin CA; Department of Chemistry, Northwestern University, Evanston, Illinois 60208, USA; International Institute for Nanotechnology, Northwestern University, Evanston, Illinois 60208, USA;
  • Stegh AH; Ken and Ruth Davee Department of Neurology, Feinberg School of Medicine, Chicago, Illinois 60611, USA; The Brain Tumor Institute, The Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, Illinois 60611, USA; Department of Chemistry, Northwestern University, Evanston, Illino
Genes Dev ; 29(7): 732-45, 2015 Apr 01.
Article em En | MEDLINE | ID: mdl-25838542
ABSTRACT
Glioblastoma multiforme (GBM) is a lethal, therapy-resistant brain cancer consisting of numerous tumor cell subpopulations, including stem-like glioma-initiating cells (GICs), which contribute to tumor recurrence following initial response to therapy. Here, we identified miR-182 as a regulator of apoptosis, growth, and differentiation programs whose expression level is correlated with GBM patient survival. Repression of Bcl2-like12 (Bcl2L12), c-Met, and hypoxia-inducible factor 2α (HIF2A) is of central importance to miR-182 anti-tumor activity, as it results in enhanced therapy susceptibility, decreased GIC sphere size, expansion, and stemness in vitro. To evaluate the tumor-suppressive function of miR-182 in vivo, we synthesized miR-182-based spherical nucleic acids (182-SNAs); i.e., gold nanoparticles covalently functionalized with mature miR-182 duplexes. Intravenously administered 182-SNAs penetrated the blood-brain/blood-tumor barriers (BBB/BTB) in orthotopic GBM xenografts and selectively disseminated throughout extravascular glioma parenchyma, causing reduced tumor burden and increased animal survival. Our results indicate that harnessing the anti-tumor activities of miR-182 via safe and robust delivery of 182-SNAs represents a novel strategy for therapeutic intervention in GBM.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Diferenciação Celular / Apoptose / Glioblastoma / MicroRNAs Tipo de estudo: Prognostic_studies Limite: Animals / Female / Humans Idioma: En Ano de publicação: 2015 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Diferenciação Celular / Apoptose / Glioblastoma / MicroRNAs Tipo de estudo: Prognostic_studies Limite: Animals / Female / Humans Idioma: En Ano de publicação: 2015 Tipo de documento: Article