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Targeting the Notch-regulated non-coding RNA TUG1 for glioma treatment

Author

Listed:
  • Keisuke Katsushima

    (Nagoya City University Graduate School of Medical Sciences)

  • Atsushi Natsume

    (Nagoya University School of Medicine)

  • Fumiharu Ohka

    (Nagoya City University Graduate School of Medical Sciences
    Nagoya University School of Medicine)

  • Keiko Shinjo

    (Nagoya City University Graduate School of Medical Sciences)

  • Akira Hatanaka

    (Nagoya City University Graduate School of Medical Sciences)

  • Norihisa Ichimura

    (Nagoya City University Graduate School of Medical Sciences)

  • Shinya Sato

    (Experimental Pathology and Tumor Biology, Nagoya City University Graduate School of Medical Sciences)

  • Satoru Takahashi

    (Experimental Pathology and Tumor Biology, Nagoya City University Graduate School of Medical Sciences)

  • Hiroshi Kimura

    (Cell Biology Unit, Institute of Innovative Research, Tokyo Institute of Technology)

  • Yasushi Totoki

    (National Cancer Center)

  • Tatsuhiro Shibata

    (National Cancer Center
    Laboratory of Molecular Medicine, Human Genome Center, The Institute of Medical Science, The University of Tokyo)

  • Mitsuru Naito

    (Center for Disease Biology and Integrative Medicine, Graduate School of Medicine, The University of Tokyo)

  • Hyun Jin Kim

    (Center for Disease Biology and Integrative Medicine, Graduate School of Medicine, The University of Tokyo)

  • Kanjiro Miyata

    (Center for Disease Biology and Integrative Medicine, Graduate School of Medicine, The University of Tokyo
    Graduate School of Engineering, The University of Tokyo)

  • Kazunori Kataoka

    (Center for Disease Biology and Integrative Medicine, Graduate School of Medicine, The University of Tokyo
    Graduate School of Engineering, The University of Tokyo
    Innovation Center of Nanomedicine, Kawasaki Institute of Industry Promotion)

  • Yutaka Kondo

    (Nagoya City University Graduate School of Medical Sciences
    Precursory Research for Embryonic Science and Technology (PRESTO), Japan Science and Technology Agency)

Abstract

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.

Suggested Citation

  • Keisuke Katsushima & Atsushi Natsume & Fumiharu Ohka & Keiko Shinjo & Akira Hatanaka & Norihisa Ichimura & Shinya Sato & Satoru Takahashi & Hiroshi Kimura & Yasushi Totoki & Tatsuhiro Shibata & Mitsur, 2016. "Targeting the Notch-regulated non-coding RNA TUG1 for glioma treatment," Nature Communications, Nature, vol. 7(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms13616
    DOI: 10.1038/ncomms13616
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    Cited by:

    1. Miho M. Suzuki & Kenta Iijima & Koichi Ogami & Keiko Shinjo & Yoshiteru Murofushi & Jingqi Xie & Xuebing Wang & Yotaro Kitano & Akira Mamiya & Yuji Kibe & Tatsunori Nishimura & Fumiharu Ohka & Ryuta S, 2023. "TUG1-mediated R-loop resolution at microsatellite loci as a prerequisite for cancer cell proliferation," Nature Communications, Nature, vol. 14(1), pages 1-20, December.

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