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

2015 Fiscal Year Final Research Report

• Project/Area Number: 26870877
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Tumor therapeutics; Biological pharmacy
• Research Institution: National 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
• 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.

Free Research Field

乳がん、抗ガン剤耐性