MiR-375 impairs breast cancer cell stemness by targeting the KLF5/G6PD signaling axis.

Recurrence of breast cancer may be due to the presence of breast cancer stem cells (BCSC). Abnormal tumor cell growth is closely associated with increased reactive oxygen species (ROS) and disruption of redox homeostasis, and BCSCs exhibit low levels of ROS. The detailed mechanism between the low levels of ROS in BCSCs and their maintenance of stemness characteristics has not been reported. A growing number of studies have shown that tumor development is often accompanied by metabolic reprogramming, which is an important hallmark of tumor cells. As the first rate-limiting enzyme of pentose phosphate pathway (PPP), the expression of G6PD is precisely regulated in tumor cells, and there is a certain correlation between PPP and BCSCs. MiR-375 has been shown to inhibit stem cell-like properties in breast cancer, but the exact mechanism is not clear. Here, KLF5, as a transcription factor, was identified to bind to the promoter of G6PD to promote its expression, whereas miR-375 inhibited the expression of KLF5 by binding to the 3'UTR region of KLF5 mRNA and thus reduced the expression of G6PD expression, inhibits PPP to reduce NADPH, and increases ROS levels in breast cancer cells, thereby weakening breast cancer cell stemness. Our study reveals the specific mechanism by which miR-375 targets the KLF5/G6PD signaling axis to diminish the stemness of breast cancer cells, providing a therapeutic strategy against BCSCs.

MicroRNA-10b regulates proliferation, cell cycle and apoptosis in human breast cancer cells / 中国药科大学学报

@#To investigate the effects of miRNA-10b(miR-10b)on breast cancer proliferation and apoptosis in MCF-7 and MDA-MB-231, the miR-10b mimics used to increase the endogenous expression of miR-10b, and miR-10b inhibitor used to decrease the endogenous expression of miR-10b, were stably transfected into MCF-7 and MDA-MB-231 breast cancer cells. The expression level of miR-10b was determined by real-time PCR. The effects of miR-10b on proliferation were evaluated by MTT assay, while cell cycle assay and the apoptosis rate were measured by flow cytometry. Bioinformatic software was used to predict the potential targets of miR-10b, and 3′UTR luciferase reporter and qRT-PCR assay were used to verify a direct target of miR-10b. The expression levels of caspase-3 and p21 protein were measured by Western blot. Results confirmed that over-expression of miR-10b could promote the proliferation of breast cancer cells and inhibit the apoptosis by up-regulating the endogenous miR-10b, while the miR-10b inhibitor could restrain the proliferation of breast cancer cells and increase the apoptosis by reducing the endogenous miR-10b. In conclusion, miR-10b could negatively regulate the expression of caspase-3 and p21 by targeting TP53INP1, hence highlighting its potential as an oncogene in breast cancer cells.