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A cluster of noncoding RNAs activates the ESR1 locus during breast cancer adaptation

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Listed:
  • Saori Tomita

    (Institute of Molecular Embryology and Genetics, Kumamoto University
    Graduate School of Medical Sciences, Kumamoto University)

  • Mohamed Osama Ali Abdalla

    (Institute of Molecular Embryology and Genetics, Kumamoto University)

  • Saori Fujiwara

    (Institute of Molecular Embryology and Genetics, Kumamoto University
    Graduate School of Medical Sciences, Kumamoto University)

  • Haruka Matsumori

    (Institute of Molecular Embryology and Genetics, Kumamoto University)

  • Kazumitsu Maehara

    (Faculty of Medicine, Kyushu University)

  • Yasuyuki Ohkawa

    (Faculty of Medicine, Kyushu University)

  • Hirotaka Iwase

    (Graduate School of Medical Sciences, Kumamoto University)

  • Noriko Saitoh

    (Institute of Molecular Embryology and Genetics, Kumamoto University)

  • Mitsuyoshi Nakao

    (Institute of Molecular Embryology and Genetics, Kumamoto University
    Program for Leading Graduate Schools ‘HIGO (Health life science: Interdisciplinary and Glocal Oriented) Program’, Kumamoto University
    Core Research for Evolutional Science and Technology (CREST), Japan Science and Technology Agency)

Abstract

Estrogen receptor-α (ER)-positive breast cancer cells undergo hormone-independent proliferation after deprivation of oestrogen, leading to endocrine therapy resistance. Up-regulation of the ER gene (ESR1) is critical for this process, but the underlying mechanisms remain unclear. Here we show that the combination of transcriptome and fluorescence in situ hybridization analyses revealed that oestrogen deprivation induced a cluster of noncoding RNAs that defined a large chromatin domain containing the ESR1 locus. We termed these RNAs as Eleanors (ESR1 locus enhancing and activating noncoding RNAs). Eleanors were present in ER-positive breast cancer tissues and localized at the transcriptionally active ESR1 locus to form RNA foci. Depletion of one Eleanor, upstream (u)-Eleanor, impaired cell growth and transcription of intragenic Eleanors and ESR1 mRNA, indicating that Eleanors cis-activate the ESR1 gene. Eleanor-mediated gene activation represents a new type of locus control mechanism and plays an essential role in the adaptation of breast cancer cells.

Suggested Citation

  • Saori Tomita & Mohamed Osama Ali Abdalla & Saori Fujiwara & Haruka Matsumori & Kazumitsu Maehara & Yasuyuki Ohkawa & Hirotaka Iwase & Noriko Saitoh & Mitsuyoshi Nakao, 2015. "A cluster of noncoding RNAs activates the ESR1 locus during breast cancer adaptation," Nature Communications, Nature, vol. 6(1), pages 1-15, November.
    • Handle: RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms7966
    DOI: 10.1038/ncomms7966
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