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NPJ Breast Cancer. 2018 Aug 6;4:20. doi: 10.1038/s41523-018-0073-7. eCollection 2018.

MiR-221/222 promote epithelial-mesenchymal transition by targeting Notch3 in breast cancer cell lines.

Liang YK#1,2,3, Lin HY#2,4, Dou XW1,2, Chen M2, Wei XL2,5, Zhang YQ1,2, Wu Y1,2, Chen CF2,4, Bai JW1,2, Xiao YS1,2, Qi YZ1,2, Kruyt FAE3, Zhang GJ1,2,6.

Author information

1
1The Breast Center, Cancer Hospital of Shantou University Medical College, 7 Raoping Road, 515031 Shantou, China.
2
2ChangJiang Scholar's Laboratory, Shantou University Medical College, 22 Xinling Road, 515041 Shantou, China.
3
Department of Medical Oncology, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9713 GZ Groningen, The Netherlands.
4
4Department of Breast and Thyroid Surgery, The First Affiliated Hospital of Shantou University Medical College (SUMC), 57 Chang ping Road, 515041 Shantou, China.
5
5Department of Pathology, The Cancer Hospital of Shantou University Medical College (SUMC), 7 Raoping Road, 515031 Shantou, China.
6
6Xiang'an Hospital of Xiamen University, 2000 East Xiang'an Rd., Xiamen, China.
#
Contributed equally

Abstract

Basal-like breast cancer (BLBC) is an aggressive subtype with a strong tendency to metastasize. Due to the lack of effective chemotherapy, BLBC has a poor prognosis compared with luminal subtype breast cancer. MicroRNA-221 and -222 (miR-221/222) are overexpressed in BLBC and associate with metastasis as well as poor prognosis; however, the mechanisms by which miR-221/222 function as oncomiRs remain unknown. Here, we report that miR-221/222 expression is inversely correlated with Notch3 expression in breast cancer cell lines. Notch3 is known to be overexpressed in luminal breast cancer cells and inhibits epithelial to mesenchymal transition (EMT). We demonstrate that miR-221/222 target Notch3 by binding to its 3' untranslated region and suppressing protein translation. Ectopic expression of miR-221/222 significantly promotes EMT, whereas overexpression of Notch3 intracellular domain attenuates the oncogenic function of miR-221/222, suggesting that miR-221/222 exerts its oncogenic role by negatively regulating Notch3. Taken together, our results elucidated that miR-221/222 promote EMT via targeting Notch3 in breast cancer cell lines suggesting that miR-221/222 can serve as a potential therapeutic target in BLBC.

Conflict of interest statement

The authors declare no competing interests.

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