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Identification of microRNA-27b as a master regulator for breast cancer stem cell generation

Research Project

Project/Area Number 26870877
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Tumor therapeutics
Biological pharmacy
Research InstitutionNational Cancer Center Japan

Principal Investigator

Ryou-u Takahashi  国立研究開発法人国立がん研究センター, その他部局等, 研究員 (10625510)

Project Period (FY) 2014-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywordsがん治療 / 乳がん / microRNA / がん幹細胞
Outline of Final Research Achievements

In the present study, we identified microRNA-27b (miR-27b) as a key regulator for the generation of cancer stem cells (CSCs). In breast caner, down-regulation of miR-27b induced the generation of side-population that shows CSC properties such as drug resistance and high tumorigenicity. MiR-27b reduced the side-population via direct repression of ectonucleotide pyrophosphatase 1 (ENPP1), which is involved in type II diabetes (T2D) development. ENPP1 induced the generation of the side-population by promoting the expression and cell surface localization of ABCG2. More importantly, a significant correlation between ENPP1 expression and breast tumor malignancy in clinical samples was observed. Overall, our study demonstrates that a T2D-associated gene plays an important role in the regulation of CSC properties and suggests that conventional chemotherapy with modulating miR-27b expression by RNA-based treatments may improve the therapeutic outcomes of breast cancer patients.

Report

(3 results)
  • 2015 Annual Research Report   Final Research Report ( PDF )
  • 2014 Research-status Report
  • Research Products

    (18 results)

All 2016 2015 2014 Other

All Journal Article (9 results) (of which Int'l Joint Research: 5 results,  Peer Reviewed: 9 results,  Acknowledgement Compliant: 3 results,  Open Access: 7 results) Presentation (6 results) (of which Int'l Joint Research: 2 results,  Invited: 3 results) Remarks (3 results)

  • [Journal Article] Establishment and characterization of an in vitro model of ovarian cancer stem-like cells with an enhanced proliferative capacity2016

    • Author(s)
      Ishiguro T, Sato A, Ohata H, Ikarashi Y, Takahashi R, Ochiya T, Yoshida M, Tsuda H, Onda T, Kato T, Kasamatsu T, Enomoto T, Tanaka K, Nakagama H, Okamoto K.
    • Journal Title

      Cancer Research

      Volume: 76 Issue: 1 Pages: 150

    • DOI

      10.1158/0008-5472.can-15-0361

    • URL

      https://localhost/en/publications/72ae941f-9bf1-4237-bcbc-0368f1b8b005

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Identification and characterization of CXCR4-positive gastric cancer stem cells2015

    • Author(s)
      Fujita T, Komatsu M, et al
    • Journal Title

      PLoS One

      Volume: 10 Issue: 6 Pages: 1-19

    • DOI

      10.1371/journal.pone.0130808

    • URL

      https://pure.teikyo.jp/en/publications/a6e67427-cb58-4e8f-90ca-62a518a64319

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Loss of microRNA-27b contributes to breast cancer stem cell generation by activating ENPP12015

    • Author(s)
      Takahashi RU, Miyazaki H, Takeshita F, Yamamoto Y, Minoura K, Ono M, Kodaira M, Tamura K, Mori M, Ochiya T
    • Journal Title

      Nature Communications

      Volume: 6 Issue: 1 Pages: 7318-7318

    • DOI

      10.1038/ncomms8318

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Expression of ribophorin II (RPN2) in human breast cancer2015

    • Author(s)
      Makiko Ono, Hitoshi Tsuda, Takayuki Kobayashi, Fumitaka Takeshita, Ryou-u Takahashi, Kenji Tamura, Sadako Akashi-Tanaka, Tomoyuki Moriya, Tamio Yamasaki, Takayuki Kinoshita, Junji Yamamoto, Yasuhiro Fujiwara, and Takahiro Ochiya
    • Journal Title

      Pathology International

      Volume: 65 Issue: 6 Pages: 301-308

    • DOI

      10.1111/pin.12297

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] The Roles of MicroRNAs in Breast Cancer2015

    • Author(s)
      Takahashi RU, Miyazaki H, Ochiya T
    • Journal Title

      Cancers

      Volume: 7 Issue: 2 Pages: 598-616

    • DOI

      10.3390/cancers7020598

    • Related Report
      2015 Annual Research Report 2014 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] The role of microRNAs in the regulation of cancer stem cells.2014

    • Author(s)
      Takahashi RU, Miyazaki H, Ochiya T.
    • Journal Title

      Front Genet

      Volume: 4 Pages: 295-295

    • DOI

      10.3389/fgene.2013.00295

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] RPN2 Gene Confers Osteosarcoma Cell Malignant Phenotypes and Determines Clinical Prognosis.2014

    • Author(s)
      Fujiwara T, Takahashi RU, Kosaka N, Nezu Y, Kawai A, Ozaki
    • Journal Title

      Mol Ther Nucleic Acids

      Volume: 3 Pages: e189-e189

    • DOI

      10.1038/mtna.2014.35

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Exosomes from bone marrow mesenchymal stem cells contain a microRNA that promotes dormancy in metastatic breast cancer cells.2014

    • Author(s)
      Ono M., Kosaka N., Tominaga N., Yoshioka Y., Takeshita F., Takahashi RU., Yoshida M., Tsuda H., Tamura K., and Ochiya T.
    • Journal Title

      Science Signaling

      Volume: 7(332) Issue: 332

    • DOI

      10.1126/scisignal.2005231

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Clinical relevance and therapeutic significance of microRNA-133a expression profiles and functions in malignant osteosarcoma-initiating cells.2014

    • Author(s)
      Fujiwara T, Katsuda T, Hagiwara K, Kosaka N, Yoshioka Y, Takahashi RU, Takeshita F, Kubota D, Kondo T, Ichikawa H, Yoshida A, Kobayashi E, Kawai A, Ozaki T, Ochiya T.
    • Journal Title

      Stem Cells.

      Volume: 32 Issue: 4 Pages: 959-973

    • DOI

      10.1002/stem.1618

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] Identification of microRNA-27b as a Master Regulator of Breast Cancer Stem Cell Generation2015

    • Author(s)
      Ryou-u Takahashi, Takahiro Ochiya
    • Organizer
      8th Annual World Cancer Congress-Korean Branch
    • Place of Presentation
      Busan, Republic of Korea
    • Year and Date
      2015-12-06
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 乳がんにおけるがん幹細胞形質獲得機構の解明2015

    • Author(s)
      髙橋陵宇, 宮崎裕明, 竹下文隆, 山本雄介, 小野麻紀子, 田村 研治, 落谷孝広
    • Organizer
      日本癌学会学術総会
    • Place of Presentation
      愛知県 名古屋市 熱田区熱田西町1番1号 名古屋国際会議場
    • Year and Date
      2015-10-08
    • Related Report
      2015 Annual Research Report
  • [Presentation] Loss of microRNA-27b-mediated gene repression promotes the generation of breast cancer stem cells2015

    • Author(s)
      Ryou-u Takahashi, Takahiro Ochiya
    • Organizer
      Molecular Medicine and Diagnostics
    • Place of Presentation
      Stockley Rd, Drayton, London UB7 9NA
    • Year and Date
      2015-08-23
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Loss of MicroRNA-27b-mediated Gene Repression Promotes Generation of Breast Cancer Stem Cells2014

    • Author(s)
      Ryou-u Takahashi, Hiroaki Miyazaki, Takahiro Ochiya
    • Organizer
      19th World Congress on Advances in Oncology and 17th International Symposium on Molecular Medicine
    • Place of Presentation
      アテネ
    • Year and Date
      2014-10-07 – 2014-10-12
    • Related Report
      2014 Research-status Report
    • Invited
  • [Presentation] 乳がんにおける幹細胞形質を制御する因子の同定とその機能解析2014

    • Author(s)
      高橋陵宇, 宮崎裕明, 竹下文隆, 小野麻紀子, 田村研治, 落谷孝広
    • Organizer
      第73回日本癌学会学術総会
    • Place of Presentation
      横浜
    • Year and Date
      2014-09-25 – 2014-09-27
    • Related Report
      2014 Research-status Report
  • [Presentation] Identification of microRNA-27b as a master regulator generating breast cancer stem cells2014

    • Author(s)
      Ryou-u Takahashi, Hiroaki Miyazaki, Takahiro Ochiya
    • Organizer
      European Molecular Biology Laboratory:「Tumour microenvironment and signalling」
    • Place of Presentation
      ドイツ
    • Year and Date
      2014-05-07 – 2014-05-11
    • Related Report
      2014 Research-status Report
  • [Remarks] 国立がん研究センター プレスリリース

    • URL

      http://www.ncc.go.jp/jp/information/press_release_20150615.html

    • Related Report
      2015 Annual Research Report
  • [Remarks] 国立がん研究センター 分子細胞治療研究分野

    • URL

      http://www.nccri.ncc.go.jp/s013/index.html

    • Related Report
      2015 Annual Research Report
  • [Remarks] 国立がん研究センター・研究所 分子細胞治療研究分野のホームページ

    • URL

      http://mcm.ncc.go.jp

    • Related Report
      2014 Research-status Report

URL: 

Published: 2014-04-04   Modified: 2017-05-10  

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