MiR-375 inhibits the sternness of breast cancer cells by blocking the JAK2/STAT3 signaling

被引:30
作者
Zhao, Qiong [1 ]
Liu, Yichen [1 ]
Wang, Ting [1 ]
Yang, Yue [1 ]
Ni, Haiwei [1 ]
Liu, Hai [1 ]
Guo, Qianqian [2 ]
Xi, Tao [1 ]
Zheng, Lufeng [1 ]
机构
[1] China Pharmaceut Univ, Sch Life Sci & Technol, Jiangsu Key Lab Carcinogenesis & Intervent, Longmian Rd 639, Nanjing 211198, Peoples R China
[2] Zhengzhou Univ, Henan Canc Hosp, Affiliated Canc Hosp, Dept Pharm, 127 Dongming Rd, Zhengzhou 450003, Peoples R China
基金
中国国家自然科学基金;
关键词
miR-375; JAK2/STAT3; Cancer stem cells; Adriamycin resistance; STEM-CELL; MESENCHYMAL TRANSITION; TAMOXIFEN RESISTANCE; MICRORNA-375; INVASION; PATHWAY;
D O I
10.1016/j.ejphar.2020.173359
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
The relapse of breast cancer could be due to the existence of breast cancer stem cells (BCSCs). Other and our researches have indicated the suppressive roles of miR-375 in various tumors, however, its roles in breast cancer stemness remain confusing. Here, we constructed breast cancer cells with miR-375 stable overexpression via lentivirus infection. Flow cytometry, Western blot, mammosphere formation, cell colony formation and CCK8 as well as in vivo assays were performed to identify the role of miR-375 in the stemness of breast cancer cells. Luciferase reporter, RNA-Fluorescence in situ hybridization (RNA-FISH) and RNA-binding protein immunoprecipitation (RIP) assays were utilized to elucidate the mechanism whereby miR-375 exerts its effects. It was found that miR-375 not only reduced the stemness, but also decreased adriamycin resistance of breast cancer cells. These results were characterized by the decrease of BCSC rate, mammosphere-forming and tumor-initiating ability, and IC50 value of adriamycin, and weakened by JAK2 re-expression. This work indicates that miR-375 suppresses the stemness of breast cancer cells through targeting JAK2.
引用
收藏
页数:10
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