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CRISPR-Cas knockout of miR21 reduces glioma growth.
Nieland, Lisa; van Solinge, Thomas S; Cheah, Pike See; Morsett, Liza M; El Khoury, Joseph; Rissman, Joseph I; Kleinstiver, Benjamin P; Broekman, Marike L D; Breakefield, Xandra O; Abels, Erik R.
Afiliación
  • Nieland L; Departments of Neurology and Radiology, Massachusetts General Hospital, Neuroscience Program, Harvard Medical School, Boston, MA 02129, USA.
  • van Solinge TS; Department of Neurosurgery, Leiden University Medical Center, 2300 RC Leiden, the Netherlands.
  • Cheah PS; Departments of Neurology and Radiology, Massachusetts General Hospital, Neuroscience Program, Harvard Medical School, Boston, MA 02129, USA.
  • Morsett LM; Departments of Neurology and Radiology, Massachusetts General Hospital, Neuroscience Program, Harvard Medical School, Boston, MA 02129, USA.
  • El Khoury J; Department of Human Anatomy, Faculty of Medicine and Health Sciences, University Putra Malaysia, Serdang 43400, Malaysia.
  • Rissman JI; Center for Immunology and Inflammatory Diseases, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02129, USA.
  • Kleinstiver BP; Center for Immunology and Inflammatory Diseases, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02129, USA.
  • Broekman MLD; Center for Genomic Medicine and Department of Pathology, Massachusetts General Hospital, Boston, MA 02115, USA.
  • Breakefield XO; Center for Genomic Medicine and Department of Pathology, Massachusetts General Hospital, Boston, MA 02115, USA.
  • Abels ER; Department of Pathology, Harvard Medical School, Boston, MA 02114, USA.
Mol Ther Oncolytics ; 25: 121-136, 2022 Jun 16.
Article en En | MEDLINE | ID: mdl-35572197
Non-coding RNAs, including microRNAs (miRNAs), support the progression of glioma. miR-21 is a small, non-coding transcript involved in regulating gene expression in multiple cellular pathways, including the regulation of proliferation. High expression of miR-21 has been shown to be a major driver of glioma growth. Manipulating the expression of miRNAs is a novel strategy in the development of therapeutics in cancer. In this study we aimed to target miR-21. Using CRISPR genome-editing technology, we disrupted the miR-21 coding sequences in glioma cells. Depletion of this miRNA resulted in the upregulation of many downstream miR-21 target mRNAs involved in proliferation. Phenotypically, CRISPR-edited glioma cells showed reduced migration, invasion, and proliferation in vitro. In immunocompetent mouse models, miR-21 knockout tumors showed reduced growth resulting in an increased overall survival. In summary, we show that by knocking out a key miRNA in glioma, these cells have decreased proliferation capacity both in vitro and in vivo. Overall, we identified miR-21 as a potential target for CRISPR-based therapeutics in glioma.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Mol Ther Oncolytics Año: 2022 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Mol Ther Oncolytics Año: 2022 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos