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

doi:10.1038/ncomms8318

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

Research output: Contribution to journal › Article › peer-review

112 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 language	English
Article number	7318
Journal	Nature communications
Volume	6
DOIs	https://doi.org/10.1038/ncomms8318
Publication status	Published - Jun 12 2015
Externally published	Yes

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

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This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1038/ncomms8318

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@article{c559d95620474d74ba0cd038fc80a383,

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

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.",

author = "Takahashi, {Ryou U.} and Hiroaki Miyazaki and Fumitaka Takeshita and Yusuke Yamamoto and Kaho Minoura and Makiko Ono and Makoto Kodaira and Kenji Tamura and Masaki Mori and Takahiro Ochiya",

note = "Funding Information: We thank Dr Kouya Shiraishi and Ms Ayako Inoue for their excellent technical assistance. This study was supported in part by a Grant-in-Aid for Young Scientists B (26870877); the Third-Term Comprehensive 10-Year Strategy for Cancer Control of Japan; a Grant-in-Aid for Scientific Research on Priority Areas Cancer from the Japanese Ministry of Education, Culture, Sports, Science and Technology; the Program for Promotion of Fundamental Studies in Health Sciences of the National Institute of Biomedical Innovation of Japan and the Funding Program for World-Leading Innovative R&D on Science and Technology (FIRST Program) from the Japan Society for the Promotion of Science (JSPS). The study was also supported by the Japan Agency for Medical Research and Development (AMED). Publisher Copyright: {\textcopyright} 2015 Macmillan Publishers Limited. All rights reserved.",

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month = jun,

day = "12",

doi = "10.1038/ncomms8318",

language = "English",

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journal = "Nature Communications",

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T1 - Loss of microRNA-27b contributes to breast cancer stem cell generation by activating ENPP1

AU - Takahashi, Ryou U.

AU - Miyazaki, Hiroaki

AU - Takeshita, Fumitaka

AU - Yamamoto, Yusuke

AU - Minoura, Kaho

AU - Ono, Makiko

AU - Kodaira, Makoto

AU - Tamura, Kenji

AU - Mori, Masaki

AU - Ochiya, Takahiro

N1 - Funding Information: We thank Dr Kouya Shiraishi and Ms Ayako Inoue for their excellent technical assistance. This study was supported in part by a Grant-in-Aid for Young Scientists B (26870877); the Third-Term Comprehensive 10-Year Strategy for Cancer Control of Japan; a Grant-in-Aid for Scientific Research on Priority Areas Cancer from the Japanese Ministry of Education, Culture, Sports, Science and Technology; the Program for Promotion of Fundamental Studies in Health Sciences of the National Institute of Biomedical Innovation of Japan and the Funding Program for World-Leading Innovative R&D on Science and Technology (FIRST Program) from the Japan Society for the Promotion of Science (JSPS). The study was also supported by the Japan Agency for Medical Research and Development (AMED). Publisher Copyright: © 2015 Macmillan Publishers Limited. All rights reserved.

PY - 2015/6/12

Y1 - 2015/6/12

N2 - 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.

AB - 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.

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

Abstract

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