MiR-124 reversed the doxorubicin resistance of breast cancer stem cells through STAT3/HIF-1 signaling pathways.

Various drug treatments including doxorubicin (DOX) have been proved efficient in the suppression of breast cancer. Nonetheless, drug resistance became an obstacle in the therapeutic process. According to recent literatures, breast cancer stem cells (BCSCs) were considered contributing to drug resistance, besides, microRNAs (miRNAs) could regulate proteins associated with drug resistance in human breast cancer. To further understand the inner mechanism of drug resistance in breast cancer and look for remedy methods, we referred to bioinformatic analysis and predicted that signal transducer and activator of transcription 3 (STAT3) and miR-124 was overexpressed in MCF7-R cells (MCF7 cells resistant to DOX) compared with MCF cells. Expression levels of RNA and protein were separately determined by qRT-PCR and western blot. Dual luciferase assay was performed to verify the targeting relationship between STAT3 and miR-124. Optical density (OD) values and apoptotic rates of cells were respectively determined via MTT assays and flow cytometric analysis. Cell invasion was detected to verify drug resistance. Results of above assays indicated that STAT3 was highly expressed in MCF7-R cells than in MCF7 cell lines and affected doxorubicin resistance of BCSCs, and miR-124 reversed the doxorubicin resistance of breast cancer stem cells through targeting STAT3 to control the HIF-1 signaling pathway. To conclude, this research may be valuable for the treatment of breast cancer as the restoration of miR-124 and inhibition of STAT3 could be applied to therapeutic strategy and help overcome drug resistance.