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MiR-489 regulates chemoresistance in breast cancer via epithelial mesenchymal transition pathway
Authors:Li Jiang  Dongxu He  Dantong Yang  Zhen Chen  Qiongxi Pan  Aiqin Mao  Yanfei Cai  Xiyuan Li  Hui Xing  Mei Shi  Yun Chen  Iain C Bruce  Teng Wang  Linfang Jin  Xiaowei Qi  Dong Hua  Jian Jin  Xin Ma
Institution:1. School of Pharmaceutical Sciences, Jiangnan University, 1800 Lihu Rd, Wuxi, Jiangsu 214122, China;2. National Engineering Laboratory for Cereal Fermentation Technology, Jiangnan University, Wuxi 214122, China;3. Affiliated Hospital, Jiangnan University, Wuxi, China
Abstract:To investigate the role of microRNAs in the development of chemoresistance and related epithelial–mesenchymal transition (EMT), we examined the effect of miR-489 in adriamycin (ADM)-resistant human breast cancer cells (MCF-7/ADM). MiR-489 was significantly suppressed in MCF-7/ADM cells compared with chemosensitive parental control MCF-7/WT cells. Forced-expression of miR-489 reversed chemoresistance. Furthermore, Smad3 was identified as the target of miR-489 and is highly expressed in MCF-7/ADM cells. Forced expression of miR-489 both inhibited Smad3 expression and Smad3 related EMT properties. Finally, the interactions between Smad3, miR-489 and EMT were confirmed in chemoresistant tumor xenografts and clinical samples, indicating their potential implication for treatment of chemoresistance.
Keywords:microRNAs  Chemoresistance  Breast cancer  Epithelial mesenchymal transition
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