Puerarin Decreases the Expression of FUS‐Dependent MAPK4 to Inhibit the Development of Triple‐Negative Breast Cancer

ABSTRACT Puerarin has been reported to have anticancer properties; however, its mechanism in regulating triple‐negative breast cancer (TNBC) remains unclear. Cell function was assessed using a cell counting kit‐8 assay, 5‐ethynyl‐2′‐deoxyuridine assay, flow cytometry, and transwell assay. Additionally, the glucose assay kit, lactate assay kit, and ADP/ATP ratio assay kit were used to analyze glucose metabolism. mRNA and protein expression levels were analyzed using qRT‐PCR and western blotting assays, respectively. The relationship between FUS RNA binding protein (FUS) and mitogen‐activated protein kinase 4 (MAPK4) was determined using an RNA immunoprecipitation assay. TNBC cell malignancy in vitro was validated using a xenograft mouse model assay. Puerarin treatment or MAPK4 knockdown effectively inhibited TNBC cell proliferation, invasion, and glucose metabolism, and induced cell apoptosis. Additionally, puerarin treatment downregulated MAPK4 and FUS expression. Conversely, MAPK4 overexpression attenuated the effects of puerarin in TNBC cells. FUS stabilized MAPK4 mRNA expression in TNBC cells. Furthermore, puerarin decreased MAPK4 expression by downregulating FUS in TNBC cells. Finally, puerarin inhibited tumor formation in vivo. Puerarin inhibited TNBC development by decreasing the expression of FUS‐dependent MAPK4, indicating that puerarin may serve as a promising therapeutic agent to hind TNBC.