Epsin 3 potentiates the NF-κB signaling pathway to regulate apoptosis in breast cancer

Endocrine drug resistance is common in some patients with estrogen receptor (ER)-positive breast cancer, so it is necessary to identify potential therapeutic targets. The aim of the present study was to investigate the regulatory effect and mechanism of epsin 3 (EPN3) expression level changes on the proliferation and apoptosis of ER-positive breast cancer. Online GEPIA was used to analyze the expression level of EPN3 in breast cancer. The online Kaplan-Meier plotter tool was used to analyze the relationship between EPN3 expression and the prognosis of patients with breast cancer. Reverse transcription-quantitative PCR, immunohistochemistry and western blotting were performed to detect the mRNA and protein expression levels of EPN3 in breast cancer tissues and cells. A lentiviral infection system was used to knockdown the expression of EPN3 in breast cancer cell lines. Cell Counting Kit-8 and flow cytometry assays were conducted to detect the effect of EPN3 knockdown on breast cancer cell proliferation and apoptosis. Western blotting was used to detect the regulation of EPN3 expression on NF-kappa B, and immunofluorescence was performed to detect the effect of EPN3 expression on NF-kappa B nuclear translocation. The results demonstrated that the expression level of EPN3 in breast cancer tissues was higher compared with that in adjacent tissues (P<0.05). The expression level of EPN3 in the ER-positive breast cancer cell line, MCF7, was higher compared with that in the other cell lines (MCF10A, ZR75-1, MDA-MB-231, BT549 and SK-BR-3). After knocking down the expression of EPN3 in MCF7 cells, the proliferative ability of the cells was decreased, and the apoptosis rate was increased (P<0.05). After EPN3 knockdown in MCF7 cells, the phosphorylation of NF-kappa B was decreased (P<0.05), and the nuclear translocation signal was weakened. Thus, it was suggested that EPN3 promoted cell proliferation and inhibited cell apoptosis by regulating the NF-kappa B signaling pathway in ER-positive breast cancer.

Automated summary

This study found that EPN3 is upregulated in ER-positive breast cancer. Knockdown of EPN3 expression can inhibit cell proliferation and promote cell apoptosis. EPN3 exerts its effects by regulating the NF-kappa B signaling pathway.