MiR-375 inhibits the stemness of breast cancer cells by blocking the JAK2/STAT3 signaling
Qiong Zhao, Yichen Liu, Ting Wang, Yue Yang, Haiwei Ni, Hai Liu, Qianqian Guo, Tao Xi, Lufeng Zheng
Journal:EUROPEAN JOURNAL OF PHARMACOLOGY
IF:3.26
DOI:10.1016/j.ejphar.2020.173359
PMID:32738343
Published:2020-07-30
research field:肿瘤学分子生物学癌症研究
Abstract
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 IC 50 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.
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