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Loss of microRNA-27b contributes to breast cancer stem cell generation by activating ENPP1

Author

Listed:
  • Ryou-u Takahashi

    (National Cancer Center Research Institute)

  • Hiroaki Miyazaki

    (National Cancer Center Research Institute)

  • Fumitaka Takeshita

    (National Cancer Center Research Institute)

  • Yusuke Yamamoto

    (National Cancer Center Research Institute)

  • Kaho Minoura

    (Genomic Application Group, Japan Diagnostics and Genomics, Agilent Technologies Japan Ltd., 9-1)

  • Makiko Ono

    (National Cancer Center Research Institute)

  • Makoto Kodaira

    (National Cancer Center Hospital, 1-1)

  • Kenji Tamura

    (National Cancer Center Hospital, 1-1)

  • Masaki Mori

    (Graduated School of Medicine, Osaka University)

  • Takahiro Ochiya

    (National Cancer Center Research Institute)

Abstract

Cancer stem cells (CSCs) have been identified in various types of cancer; however, the mechanisms by which cells acquire CSC properties such as drug resistance and tumour seeding ability are not fully understood. Here, we identified microRNA-27b (miR-27b) as a key regulator for the generation of a side-population in breast cancer cells that showed CSC properties, and also found that the anti-type II diabetes (T2D) drug metformin reduced this side-population via miR-27b-mediated repression of ectonucleotide pyrophosphatase/phosphodiesterase family member 1 (ENPP1), which is involved in T2D development. ENPP1 induced the generation of the side-population via upregulation of the ABCG2 transporter. ENPP1 was also identified as a substrate of the 26S proteasome, the activity of which is downregulated in CSCs. Overall, these results demonstrate that a T2D-associated gene plays an important role in tumour development and that its expression is strictly controlled at the mRNA and protein levels.

Suggested Citation

  • Ryou-u Takahashi & Hiroaki Miyazaki & Fumitaka Takeshita & Yusuke Yamamoto & Kaho Minoura & Makiko Ono & Makoto Kodaira & Kenji Tamura & Masaki Mori & Takahiro Ochiya, 2015. "Loss of microRNA-27b contributes to breast cancer stem cell generation by activating ENPP1," Nature Communications, Nature, vol. 6(1), pages 1-15, November.
    • Handle: RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms8318
    DOI: 10.1038/ncomms8318
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