期刊
SCIENTIFIC REPORTS
卷 5, 期 -, 页码 -出版社
NATURE PORTFOLIO
DOI: 10.1038/srep13170
关键词
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资金
- Ministry of Education, Culture, Sports, Science, and Technology, Japan
- Japan Society for the Promotion of Science, Japan [23249040, 15K15353]
- Ministry of Health, Labour, and Welfare, Japan
- Advanced Research for Medical Products Mining Program of the National Institute of Biomedical Innovation, Japan
- Grants-in-Aid for Scientific Research [15K15353, 26293223, 23249040] Funding Source: KAKEN
Breast cancer is a hormone-dependent cancer and usually treated with endocrine therapy using aromatase inhibitors or anti-estrogens such as tamoxifen. A majority of breast cancer, however, will often fail to respond to endocrine therapy. In the present study, we explored miRNAs associated with endocrine therapy resistance in breast cancer. High-throughput miRNA sequencing was performed using RNAs prepared from breast cancer MCF-7 cells and their derivative clones as endocrine therapy resistant cell models, including tamoxifen-resistant (TamR) and long-term estrogen-deprived (LTED) MCF-7 cells. Notably, miR-21 was the most abundantly expressed miRNA in MCF-7 cells and overexpressed in TamR and LTED cells. We found that miR-378a-3p expression was downregulated in TamR and LTED cells as well as in clinical breast cancer tissues. Additionally, lower expression levels of miR-378a-3p were associated with poor prognosis for tamoxifen-treated patients with breast cancer. GOLT1A was selected as one of the miR-378a-3p candidate target genes by in silico analysis. GOLT1A was overexpressed in breast cancer specimens and GOLT1A-specific siRNAs inhibited the growth of TamR cells. Low GOLT1A levels were correlated with better survival in patients with breast cancer. These results suggest that miR-378a-3p-dependent GOLT1A expression contributes to the mechanisms underlying breast cancer endocrine resistance.
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