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

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 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.

Keywords: Adriamycin resistance; Cancer stem cells; JAK2/STAT3; miR-375.