EZH2 induces the expression of miR-1301 as a negative feedback control mechanism in triple negative breast cancer.

Breast cancer is one of the most common malignancies in women. ERα, PR, and HER2 triple negative breast cancer (TNBC) is the current research focus because of the lack of effective targeted therapies. In our study, lentivirus systems were used to overexpress EZH2 and miR-1301 in TNBC cell lines. Western blot analysis and RT-qPCR were used to detect the protein and microRNA levels. The TCGA and Kaplan Meier plotter databases were used to analyze the EZH2 and miR-1301 expression levels in breast cancer. The effect of miR-1301 overexpression on cell proliferation, migration and colony formation were determined by using the sulforhodamine B (SRB) assay, wound healing assay and colony formation assay, respectively. Furthermore, an xenograft mouse model was used to investigate the function of miR-1301 overexpression in vivo. Finally, dual luciferase reporter assay was used to verify the binding site of EZH2 and miR-1301. We found that EZH2 induced the expression of miR-1301 in two TNBC cell lines, HCC1937 and HCC1806. Overexpression of miR-1301 suppressed TNBC cell proliferation, migration and colony formation, as well as the xenograft tumor growth in immunodeficient mice. Interestingly, miR-1301 inhibited the expression of EZH2 by binding to the 3'-UTR of EZH2 gene. These data suggest that EZH2 induces the expression of miR-1301 as a negative feedback control mechanism in TNBC.