MicroRNA‐34a suppresses the breast cancer stem cell‐like characteristics by downregulating Notch1 pathway

• Published in: Cancer science 2015-06, Vol.106 (6), p.700-708
• Main Authors: Kang, Le, Mao, Jun, Tao, Yajun, Song, Bo, Ma, Wei, Lu, Ying, Zhao, Lijing, Li, Jiazhi, Yang, Baoxue, Li, Lianhong
• Format: Article
• Language: English
• Subjects: Breast cancer stem cell; Breast Neoplasms - drug therapy; Breast Neoplasms - pathology; Cell Movement; Cell Proliferation; Down-Regulation; drug resistance; Drug Resistance, Neoplasm; Humans; MCF-7 Cells; MicroRNAs - physiology; miR‐34a; Neoplasm Invasiveness; Neoplasm Staging; Neoplastic Stem Cells - physiology; Notch1; Original; paclitaxel; Paclitaxel - therapeutic use; Receptor, Notch1 - antagonists & inhibitors; Receptor, Notch1 - physiology; Signal Transduction
• ISSN: 1347-9032; 1349-7006
• DOI: 10.1111/cas.12656

MicroRNAs play pivotal roles in cancer stem cell regulation. Previous studies have shown that microRNA‐34a (miR‐34a) is downregulated in human breast cancer. However, it is unknown whether and how miR‐34a regulates breast cancer stem cells. Notch signaling is one of the most important pathways in stem cell maintenance and function. In this study, we verified that miR‐34a directly and functionally targeted Notch1 in MCF‐7 cells. We reported that miR‐34a negatively regulated cell proliferation, migration, and invasion and breast cancer stem cell propagation by downregulating Notch1. The expression of miR‐34a was negatively correlated with tumor stages, metastasis, and Notch1 expression in breast cancer tissues. Furthermore, overexpression of miR‐34a increased chemosensitivity of breast cancer cells to paclitaxel (PTX) by downregulating the Notch1 pathway. Mammosphere formation and expression of the stemness factor ALDH1 were also reduced in the cells treated with miR‐34a and PTX compared to those treated with PTX alone. Taken together, our results indicate that miR‐34a inhibited breast cancer stemness and increased the chemosensitivity to PTX partially by downregulating the Notch1 pathway, suggesting that miR‐34a/Notch1 play an important role in regulating breast cancer stem cells. Thus miR‐34a is a potential target for prevention and therapy of breast cancer. Our study showed miR‐34a was downregulated in breast cancer stem cells. Overexpression of miR‐34a may inhibit the propagation of breast cancer stem cells by targeting Notch1. MiR‐34a may increase the chemosensitivity of breast cancer stem cells to paclitaxel by modulating Notch1 pathway.