MicroRNA-361-3p promotes human breast cancer cell viability by inhibiting the E2F1/P73 signalling pathway

Abstract

Analysis of the microRNA (miRNA) expression signature of breast cancer based on RNA sequencing demonstrated that miR-361-3p was significantly upregulated in breast cancer tissues. miR-361-3p is a novel miRNA, and its role in breast cancer is currently unclear. The aim of the present study was to investigate the functions of miR-361-3p in breast carcinoma. In this study, it was observed that the expression of miR-361-3p in cancer tissues was significantly higher compared with that in para-cancerous tissues and was correlated with advanced TNM stage, Ki-67 overexpression and shorter disease-free survival. Overexpression of miR-361-3p promoted proliferation and inhibited apoptosis of breast cancer cells. Through RNA sequencing, multi-library retrieval, luciferase reporter assays, quantitative polymerase chain reaction analysis, western blotting and other methods, it was verified that E2F1 was directly downregulated by miR-361-3p. The knockdown of E2F1 by siRNA promoted breast cancer cell proliferation and inhibited apoptosis, similar to miR-361-3p. In addition, miR-361-3p was able to decrease the expression of P73 by targeting E2F1, whereas overexpression of P73 reversed the effect of miR-361-3p on the viability of breast cancer cell lines. Thus, the present study demonstrated that miR-361-3p acts as an oncomiR in breast cancer to promote proliferation and inhibit apoptosis through inhibiting the P73 pathway by downregulating E2F1 expression, which may uncover valuable prognostic factors or treatment targets.

Keywords: Apoptosis; Breast carcinoma; E2F1; P73; Proliferation; miR-361-3p.