EZH2 Induces The Expression Of MiR-1301 As A Negative Feedback Control Mechanism In Triple Negative Breast Cancer

ObjectiveBreast cancer is one of the most common malignancies in women,as one of the most malignant subtype of breast cancer,triple negative breast cancer(TNBC)is short of effective targeted therapies because of lacking effective targets.Herein,identification of sensitive therapeutic targets and develop new treatment strategies are necessary.EZH2 is a new therapeutic target for triple-negative breast cancer,but its regulatory mechanism is not yet clear.This study aims to elucidate the function and mechanism of a mi R-1301 inhibition of EZH2.MethodsAt first,lentivirus system was used to overexpress EZH2 and mi R-1301 in breast cancer.We used Western blot and RT-q PCR to detect gene expression at protein and micro RNA levels,respectively.Also,we collected data from TCGA and Kaplan Meier plotter database and analyzed the relationship between EZH2 and mi R-1301 expression and the overall survival in breast cancer.Then we used SRB,wound healing and colony formation assays to test the function of mi R-1301 in TNBC.In vivo xenograft mouse model was used.At last,dual luciferase reporter assay was used to verify the regulation of EZH2 on mi R-1301.All data were presented as mean±SD.Differences among groups were analyzed using Student's t-test.P < 0.05 was considered statistically significant.ResultsEZH2 induces the expression of mi R-1301 in TNBC cell lines.Via analyzing data from TCGA database,we found both EZH2 and mi R-1301 are highly expressed in breast cancer samples.Furthermore,the expression levels of EZH2 and mi R-1301 are positively correlated,and high expression levels of EZH2 and mi R-1301 are associated with shorter patient survival.Overexpression of mi R-1301 suppresses TNBC cell proliferation,migration and colony formation,as well as the xenograft tumor growth in immunodeficient mice.As a negative feedback,mi R-1301 inhibited the expression of EZH2 by binding to the 3'-UTR of EZH2 gene.ConclusionsEZH2 induces the expression of mi R-1301 as a negative feedback control mechanism in triple negative breast cancer.Besides,mi R-1301 functions as a tumor suppressor in triple negative breast cancer.Thus,EZH2 and mi R-1301 may be used as therapeutic targets for triple negative breast cancer.