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.

Details

Title
MiR-221/222 promote epithelial-mesenchymal transition by targeting Notch3 in breast cancer cell lines
Author
Yuan-Ke, Liang 1 ; Hao-Yu, Lin 2 ; Xiao-Wei, Dou 3 ; Chen, Min 4 ; Xiao-Long, Wei 5 ; Yong-Qu, Zhang 3 ; Wu, Yang 3 ; Chun-Fa Chen 2 ; Jing-Wen, Bai 3 ; Ying-Sheng, Xiao 3 ; Yu-Zhu, Qi 3 ; Kruyt, Frank A E 6 ; Guo-Jun, Zhang 7 

 The Breast Center, Cancer Hospital of Shantou University Medical College, Shantou, China; ChangJiang Scholar’s Laboratory, Shantou University Medical College, Shantou, China; Department of Medical Oncology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands 
 ChangJiang Scholar’s Laboratory, Shantou University Medical College, Shantou, China; Department of Breast and Thyroid Surgery, The First Affiliated Hospital of Shantou University Medical College (SUMC), Shantou, China 
 The Breast Center, Cancer Hospital of Shantou University Medical College, Shantou, China; ChangJiang Scholar’s Laboratory, Shantou University Medical College, Shantou, China 
 ChangJiang Scholar’s Laboratory, Shantou University Medical College, Shantou, China 
 ChangJiang Scholar’s Laboratory, Shantou University Medical College, Shantou, China; Department of Pathology, The Cancer Hospital of Shantou University Medical College (SUMC), Shantou, China 
 Department of Medical Oncology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands 
 The Breast Center, Cancer Hospital of Shantou University Medical College, Shantou, China; ChangJiang Scholar’s Laboratory, Shantou University Medical College, Shantou, China; Xiang’an Hospital of Xiamen University, Xiamen, China 
Pages
1-9
Publication year
2018
Publication date
Aug 2018
Publisher
Nature Publishing Group
e-ISSN
23744677
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2084332784
Copyright
© 2018. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.