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

Ryou U. Takahashi, Hiroaki Miyazaki, Fumitaka Takeshita, Yusuke Yamamoto, Kaho Minoura, Makiko Ono, Makoto Kodaira, Kenji Tamura, Masaki Mori, Takahiro Ochiya

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82 Citations (Scopus)

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.

Original languageEnglish
Article number7318
JournalNature communications
Volume6
DOIs
Publication statusPublished - Jun 12 2015
Externally publishedYes

All Science Journal Classification (ASJC) codes

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

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