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

Saori Tomita, Mohamed Osama Ali Abdalla, Saori Fujiwara, Haruka Matsumori, Kazumitsu Maehara, Yasuyuki Ohkawa, Hirotaka Iwase, Noriko Saitoh, Mitsuyoshi Nakao

研究成果: Contribution to journalArticle

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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.

元の言語英語
記事番号6966
ジャーナルNature communications
6
DOI
出版物ステータス出版済み - 4 29 2015

All Science Journal Classification (ASJC) codes

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

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    Tomita, S., Abdalla, M. O. A., Fujiwara, S., Matsumori, H., Maehara, K., Ohkawa, Y., Iwase, H., Saitoh, N., & Nakao, M. (2015). A cluster of noncoding RNAs activates the ESR1 locus during breast cancer adaptation. Nature communications, 6, [6966]. https://doi.org/10.1038/ncomms7966