TY - JOUR
T1 - MicroRNA-574-3p, identified by microRNA library-based functional screening, modulates tamoxifen response in breast cancer
AU - Ujihira, T.
AU - Ikeda, K.
AU - Suzuki, T.
AU - Yamaga, R.
AU - Sato, W.
AU - Horie-Inoue, K.
AU - Shigekawa, T.
AU - Osaki, A.
AU - Saeki, T.
AU - Okamoto, K.
AU - Takeda, S.
AU - Inoue, S.
N1 - Funding Information:
This work was supported by Grants of the Genome Network Project, Cell Innovation Program, P-DIRECT, Grants-in-Aid, and Support Project of Strategic Research Center in Private Universities from the Ministry of Education, Culture, Sports, Science, and Technology, Japan; by Grants from the Japan Society for the Promotion of Science, Japan (23249040); by Grants-in-Aid from the Ministry of Health, Labour, and Welfare, Japan; by the Advanced Research for Medical Products Mining Program of the National Institute of Biomedical Innovation, Japan.
PY - 2015/1/6
Y1 - 2015/1/6
N2 - Most primary breast cancers express estrogen receptor a and can be treated via endocrine therapy using anti-estrogens such as tamoxifen; however, acquired endocrine resistance is a critical issue. To identify tamoxifen response-related microRNAs (miRNAs) in breast cancer, MCF-7 cells infected with a lentiviral miRNA library were treated with 4-hydroxytamoxifen (OHT) or vehicle for 4 weeks, and the amounts of individual miRNA precursors that had integrated into the genome were evaluated by microarray. Compared to the vehicle-treated cells, 5 'dropout' miRNAs, which were downregulated in OHT-treated cells, and 6 'retained' miRNAs, which were upregulated in OHT-treated cells, were identified. Of the dropout miRNAs, we found that miR-574-3p expression was downregulated in clinical breast cancer tissues as compared with their paired adjacent tissues. In addition, anti-miR-574-3p reversed tamoxifen-mediated suppression of MCF-7 cell growth. Clathrin heavy chain (CLTC) was identified as a miR-574-3p target gene by in silico algorithms and luciferase reporter assay using the 39 untranslated region of CLTC mRNA. Interestingly, loss and gain of miR-574-3p function in MCF-7 cells causes CLTC to be upregulated and downregulated, respectively. These results suggest that functional screening mediated by miRNA libraries can provide new insights into the genes essential for tamoxifen response in breast cancer.
AB - Most primary breast cancers express estrogen receptor a and can be treated via endocrine therapy using anti-estrogens such as tamoxifen; however, acquired endocrine resistance is a critical issue. To identify tamoxifen response-related microRNAs (miRNAs) in breast cancer, MCF-7 cells infected with a lentiviral miRNA library were treated with 4-hydroxytamoxifen (OHT) or vehicle for 4 weeks, and the amounts of individual miRNA precursors that had integrated into the genome were evaluated by microarray. Compared to the vehicle-treated cells, 5 'dropout' miRNAs, which were downregulated in OHT-treated cells, and 6 'retained' miRNAs, which were upregulated in OHT-treated cells, were identified. Of the dropout miRNAs, we found that miR-574-3p expression was downregulated in clinical breast cancer tissues as compared with their paired adjacent tissues. In addition, anti-miR-574-3p reversed tamoxifen-mediated suppression of MCF-7 cell growth. Clathrin heavy chain (CLTC) was identified as a miR-574-3p target gene by in silico algorithms and luciferase reporter assay using the 39 untranslated region of CLTC mRNA. Interestingly, loss and gain of miR-574-3p function in MCF-7 cells causes CLTC to be upregulated and downregulated, respectively. These results suggest that functional screening mediated by miRNA libraries can provide new insights into the genes essential for tamoxifen response in breast cancer.
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U2 - 10.1038/srep07641
DO - 10.1038/srep07641
M3 - Article
C2 - 25560734
AN - SCOPUS:84934446389
VL - 5
JO - Scientific Reports
JF - Scientific Reports
SN - 2045-2322
M1 - 7641
ER -