MIR-378a-3p modulates tamoxifen sensitivity in breast cancer MCF-7 cells through targeting GOLT1A

Kazuhiro Ikeda, Kuniko Horie-Inoue, Toshihide Ueno, Takashi Suzuki, Wataru Sato, Takashi Shigekawa, Akihiko Osaki, Toshiaki Saeki, Eugene Berezikov, Hiroyuki Mano, Satoshi Inoue

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Abstract

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.

Original languageEnglish
Article number13170
JournalScientific reports
Volume5
DOIs
Publication statusPublished - 2015 Aug 10

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    Ikeda, K., Horie-Inoue, K., Ueno, T., Suzuki, T., Sato, W., Shigekawa, T., Osaki, A., Saeki, T., Berezikov, E., Mano, H., & Inoue, S. (2015). MIR-378a-3p modulates tamoxifen sensitivity in breast cancer MCF-7 cells through targeting GOLT1A. Scientific reports, 5, [13170]. https://doi.org/10.1038/srep13170