دورية أكاديمية

CRISPRi-based radiation modifier screen identifies long non-coding RNA therapeutic targets in glioma.

التفاصيل البيبلوغرافية
العنوان: CRISPRi-based radiation modifier screen identifies long non-coding RNA therapeutic targets in glioma.
المؤلفون: Liu SJ; Department of Neurological Surgery, University of California, San Francisco, CA, 94143, USA.; Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco, CA, 94143, USA.; Department of Radiation Oncology, University of California, San Francisco, CA, 94143, USA.; San Francisco Veterans Affairs Medical Center, San Francisco, CA, USA., Malatesta M; Department of Neurological Surgery, University of California, San Francisco, CA, 94143, USA.; Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco, CA, 94143, USA.; San Francisco Veterans Affairs Medical Center, San Francisco, CA, USA., Lien BV; Department of Neurological Surgery, University of California, San Francisco, CA, 94143, USA.; Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco, CA, 94143, USA.; San Francisco Veterans Affairs Medical Center, San Francisco, CA, USA., Saha P; Department of Neurological Surgery, University of California, San Francisco, CA, 94143, USA.; Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco, CA, 94143, USA.; San Francisco Veterans Affairs Medical Center, San Francisco, CA, USA., Thombare SS; Department of Neurological Surgery, University of California, San Francisco, CA, 94143, USA.; Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco, CA, 94143, USA.; San Francisco Veterans Affairs Medical Center, San Francisco, CA, USA., Hong SJ; Department of Neurological Surgery, University of California, San Francisco, CA, 94143, USA.; Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco, CA, 94143, USA.; San Francisco Veterans Affairs Medical Center, San Francisco, CA, USA.; Developmental and Stem Cell Biology Graduate Program, University of California, San Francisco, CA, 94143, USA., Pedraza L; Department of Neurological Surgery, University of California, San Francisco, CA, 94143, USA.; Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco, CA, 94143, USA.; San Francisco Veterans Affairs Medical Center, San Francisco, CA, USA., Koontz M; Department of Ophthalmology, University of California, San Francisco, CA, 94143, USA., Seo K; Department of Neurological Surgery, University of California, San Francisco, CA, 94143, USA.; Department of Radiation Oncology, University of California, San Francisco, CA, 94143, USA., Horlbeck MA; Department of Cellular and Molecular Pharmacology, University of California, San Francisco, CA, 94143, USA.; Howard Hughes Medical Institute, University of California, San Francisco, CA, 94143, USA.; California Institute for Quantitative Biomedical Research, University of California, San Francisco, CA, 94143, USA.; Center for RNA Systems Biology, University of California, San Francisco, CA, 94143, USA., He D; Department of Neurological Surgery, University of California, San Francisco, CA, 94143, USA.; Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco, CA, 94143, USA.; San Francisco Veterans Affairs Medical Center, San Francisco, CA, USA.; Developmental and Stem Cell Biology Graduate Program, University of California, San Francisco, CA, 94143, USA., Birk HS; Department of Neurological Surgery, University of California, San Francisco, CA, 94143, USA.; Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco, CA, 94143, USA.; San Francisco Veterans Affairs Medical Center, San Francisco, CA, USA., Jain M; UC Santa Cruz Genomics Institute, University of California, Santa Cruz, CA, 95064, USA., Olsen HE; UC Santa Cruz Genomics Institute, University of California, Santa Cruz, CA, 95064, USA., Akeson M; UC Santa Cruz Genomics Institute, University of California, Santa Cruz, CA, 95064, USA., Weissman JS; Department of Cellular and Molecular Pharmacology, University of California, San Francisco, CA, 94143, USA.; Howard Hughes Medical Institute, University of California, San Francisco, CA, 94143, USA.; California Institute for Quantitative Biomedical Research, University of California, San Francisco, CA, 94143, USA.; Center for RNA Systems Biology, University of California, San Francisco, CA, 94143, USA., Monje M; Department of Neurology and Neurological Sciences, Stanford University, Stanford, CA, 94305, USA., Gupta N; Department of Neurological Surgery, University of California, San Francisco, CA, 94143, USA., Raleigh DR; Department of Neurological Surgery, University of California, San Francisco, CA, 94143, USA.; Department of Radiation Oncology, University of California, San Francisco, CA, 94143, USA., Ullian EM; Department of Ophthalmology, University of California, San Francisco, CA, 94143, USA., Lim DA; Department of Neurological Surgery, University of California, San Francisco, CA, 94143, USA. Daniel.Lim@ucsf.edu.; Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco, CA, 94143, USA. Daniel.Lim@ucsf.edu.; San Francisco Veterans Affairs Medical Center, San Francisco, CA, USA. Daniel.Lim@ucsf.edu.
المصدر: Genome biology [Genome Biol] 2020 Mar 31; Vol. 21 (1), pp. 83. Date of Electronic Publication: 2020 Mar 31.
نوع المنشور: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: BioMed Central Ltd Country of Publication: England NLM ID: 100960660 Publication Model: Electronic Cited Medium: Internet ISSN: 1474-760X (Electronic) Linking ISSN: 14747596 NLM ISO Abbreviation: Genome Biol Subsets: MEDLINE
أسماء مطبوعة: Publication: London, UK : BioMed Central Ltd
Original Publication: London : Genome Biology Ltd., c2000-
مواضيع طبية MeSH: CRISPR-Cas Systems*, Brain Neoplasms/*therapy , Glioblastoma/*therapy , RNA, Long Noncoding/*antagonists & inhibitors, Adult ; Astrocytes ; Brain ; Brain Neoplasms/genetics ; Brain Neoplasms/pathology ; Brain Neoplasms/radiotherapy ; Cell Line, Tumor ; Combined Modality Therapy ; Glioblastoma/genetics ; Glioblastoma/pathology ; Glioblastoma/radiotherapy ; Humans ; Oligonucleotides, Antisense ; Organoids ; Radiation Tolerance
مستخلص: Background: Long non-coding RNAs (lncRNAs) exhibit highly cell type-specific expression and function, making this class of transcript attractive for targeted cancer therapy. However, the vast majority of lncRNAs have not been tested as potential therapeutic targets, particularly in the context of currently used cancer treatments. Malignant glioma is rapidly fatal, and ionizing radiation is part of the current standard-of-care used to slow tumor growth in both adult and pediatric patients.
Results: We use CRISPR interference (CRISPRi) to screen 5689 lncRNA loci in human glioblastoma (GBM) cells, identifying 467 hits that modify cell growth in the presence of clinically relevant doses of fractionated radiation. Thirty-three of these lncRNA hits sensitize cells to radiation, and based on their expression in adult and pediatric gliomas, nine of these hits are prioritized as lncRNA Glioma Radiation Sensitizers (lncGRS). Knockdown of lncGRS-1, a primate-conserved, nuclear-enriched lncRNA, inhibits the growth and proliferation of primary adult and pediatric glioma cells, but not the viability of normal brain cells. Using human brain organoids comprised of mature neural cell types as a three-dimensional tissue substrate to model the invasive growth of glioma, we find that antisense oligonucleotides targeting lncGRS-1 selectively decrease tumor growth and sensitize glioma cells to radiation therapy.
Conclusions: These studies identify lncGRS-1 as a glioma-specific therapeutic target and establish a generalizable approach to rapidly identify novel therapeutic targets in the vast non-coding genome to enhance radiation therapy.
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معلومات مُعتمدة: HG010053 United States NH NIH HHS; R21 NS101395 United States NS NINDS NIH HHS; T32 GM007618 United States GM NIGMS NIH HHS; 1R21 NS101395-01 United States NH NIH HHS; F30 NS092319-01 United States NH NIH HHS; I01 BX000252 United States BX BLRD VA; R01 HG010053 United States HG NHGRI NIH HHS; 1R01NS091544 United States NH NIH HHS; R03AG063157 United States NH NIH HHS; R01 NS091544 United States NS NINDS NIH HHS; T32 HD007470 United States HD NICHD NIH HHS; R03 AG063157 United States AG NIA NIH HHS; P30 EY002162 United States EY NEI NIH HHS
فهرسة مساهمة: Keywords: CRISPRi; Cancer therapy; Glioma; Organoids; Radiation; lncRNA
المشرفين على المادة: 0 (Oligonucleotides, Antisense)
0 (RNA, Long Noncoding)
تواريخ الأحداث: Date Created: 20200403 Date Completed: 20210223 Latest Revision: 20211009
رمز التحديث: 20240628
مُعرف محوري في PubMed: PMC7110660
DOI: 10.1186/s13059-020-01995-4
PMID: 32234056
قاعدة البيانات: MEDLINE
الوصف
تدمد:1474-760X
DOI:10.1186/s13059-020-01995-4