Nature communications, 2016-12, Vol.7 (1), p.13616-13616, Article 13616
2016
Details
- Autor(en) / Beteiligte
- Titel
- Targeting the Notch-regulated non-coding RNA TUG1 for glioma treatment
- Ist Teil von
- Nature communications, 2016-12, Vol.7 (1), p.13616-13616, Article 13616
- Ort / Verlag
- England: Nature Publishing Group
- Erscheinungsjahr
- 2016
- Link zum Volltext
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- Targeting self-renewal is an important goal in cancer therapy and recent studies have focused on Notch signalling in the maintenance of stemness of glioma stem cells (GSCs). Understanding cancer-specific Notch regulation would improve specificity of targeting this pathway. In this study, we find that Notch1 activation in GSCs specifically induces expression of the lncRNA, TUG1. TUG1 coordinately promotes self-renewal by sponging miR-145 in the cytoplasm and recruiting polycomb to repress differentiation genes by locus-specific methylation of histone H3K27 via YY1-binding activity in the nucleus. Furthermore, intravenous treatment with antisense oligonucleotides targeting TUG1 coupled with a drug delivery system induces GSC differentiation and efficiently represses GSC growth in vivo. Our results highlight the importance of the Notch-lncRNA axis in regulating self-renewal of glioma cells and provide a strong rationale for targeting TUG1 as a specific and potent therapeutic approach to eliminate the GSC population.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 2041-1723eISSN: 2041-1723DOI: 10.1038/ncomms13616Titel-ID: cdi_doaj_primary_oai_doaj_org_article_36464f0713394d1ea6623709d1ee83d9
- Format
- –
- Schlagworte
- Animals, Biology, Brain cancer, Brain Neoplasms - genetics, Brain Neoplasms - therapy, Carcinogenesis - genetics, Carcinogenesis - pathology, Cell Differentiation - genetics, Drug delivery systems, Enhancer of Zeste Homolog 2 Protein - metabolism, Exons - genetics, Female, Gene Expression Regulation, Neoplastic, Genes, Genomes, Glioma - genetics, Glioma - therapy, Humans, Medicine, Mice, Inbred NOD, Mice, SCID, MicroRNAs - genetics, MicroRNAs - metabolism, Neoplastic Stem Cells - metabolism, Neoplastic Stem Cells - pathology, Neurons - metabolism, Polycomb Repressive Complex 2 - metabolism, Protein Binding, Proto-Oncogene Proteins c-myc - metabolism, Receptor, Notch1 - metabolism, RNA, Long Noncoding - genetics, RNA, Long Noncoding - metabolism, RNA, Messenger - genetics, RNA, Messenger - metabolism, Science, SOXB1 Transcription Factors - metabolism, Stem cells, Xenograft Model Antitumor Assays, YY1 Transcription Factor - metabolism