MicroRNA-939 Promotes the Vitality of Human Breast Cancer Cells via Inhibition of E2F1/P73 Signaling

Abstract

We assessed miR-939’s role in breast cancer (BC) and its molecular mechanism. PCR was performed to detect miRNA levels. Correlations between miR-939 and patients’ pathological information were analyzed. After transfection of E2F1 plasmid, P73 plasmid, si-E2F1, si-P73, miR-939 mimic or si-miR-939, cell proliferation and apoptosis were measured. The miR-939 target gene was proved by a luciferase assay. Protein and mRNA levels of E2F1 and P73 were detected by immunoblotting and PCR, and corresponding proliferation or apoptosis were assessed. MiR-939 expression was significantly increased in BC and associated with TNM staging, Ki-67 enhancement, and shorter disease-free survival time. In BC clinical samples, E2F1 expression is negatively correlated with miR-939 expressions. Overexpressing miR-939 stimulated growth but suppressed cell apoptosis. Functional analysis indicated E2F1 is the target gene of miR-939, and overexpression of miR-939 significantly downregulated E2F1 and P73. Silencing of E2F1 or P73 significantly promoted MDA-MB-231 cell proliferation and inhibited apoptosis. Overexpression of E2F1 plasmid or P73 plasmid significantly inhibited MDA-MB-231 cell proliferation but induced apoptosis. Transfection of P73 or E2F1 plasmid abolished miR-939’s effects on proliferation and apoptosis. miR-939 promotes breast cancer progression by downregulation of E2F1 to inhibit P73 pathway, thereby promoting proliferation and inhibiting apoptosis.