miR-200c inhibits breast cancer proliferation by targeting KRAS
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Cailu Song1,*, Long-Zhong Liu2,*, Xiao-Qing Pei2,*, Xiaoping Liu1, Lu Yang1, Feng Ye1, Xinhua Xie1, Jianping Chen3, Hailin Tang1, Xiaoming Xie1
1Department of Breast Oncology, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong, China
2Department of Ultrasond, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong, China
3School of Chinese Medicine, The University of Hong Kong, Hong Kong
*These authors have contributed equally to this work
Xiaoming Xie, e-mail: [email protected]
Hailin Tang, e-mail: [email protected]
Keywords: microRNA, miR-200c, KRAS, breast cancer, proliferation
Abbreviations: ER, estrogen receptor; PR, progesterone receptor; HER2, human epidermal growth factor receptor-2; EGFR, epidermal growth factor receptor
Received: May 26, 2015 Accepted: August 27, 2015 Published: September 09, 2015
The microRNA, miR-200c, is involved in the tumorigenesis and progression of a variety of cancers. The purpose of this study was to investigate the expression, mechanism and prognostic roles of miR-200c in breast cancer. We found that miR-200c was downregulated in both breast cancer tissue and cell lines using quantitative real-time PCR (qRT-PCR). In situ hybridization (ISH) and microarrays showed that low miR-200c expression was associated with poor patient overall survival (OS) and disease free survival (DFS). We used luciferase reporter plasmids to find that miR-200c inhibited the AKT and ERK pathways by directly targeting KRAS. Repression of KRAS by miR-200c suppressed the proliferation and survival of breast cancer cells in vitro and in vivo. miR-200c also had an anti-tumor effect by negatively regulating KRAS in a xenograft mouse model. Our findings provide clues regarding the role of miR-200c as a tumor suppressor in breast cancer through the inhibition of KRAS translation both in vitro and in vivo. miR-200c could be a potential therapeutic target in breast cancer.
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