MiRNA-96-5p impacts the progression of breast cancer through targeting FOXO3

Abstract

Background: Breast cancer is the most common malignant tumor in women worldwide, with a high mortality rate. MicroRNAs are small non-coding RNAs that negatively regulate the expression of target genes by interacting with the target gene 3'-UTR, and participate in cell differentiation, proliferation, apoptosis and metabolism. The function of miRNA-96-5p in the progression of breast cancer has not been reported.

Methods: We used the StarBase database to investigate the expression of miRNA-96-5p in breast cancer and adjacent normal tissues. FOXO3 3'-UTR construct and luciferase reporter assays was performed for the target gene. Expression levels of miRNAs including its target were analyzed by qRT-PCR and western blot. Cell proliferation was detected by CCK8 and colony formation, EdU assay.

Results: Luciferase reporter assays showed miRNA-96-5p directly targeted FOXO3. Abrogation of miRNA-96-5p by transfection with its inhibitors in breast cancer cells significantly suppressed miRNA-96-5p expression and breast cancer cells proliferation. Western blot revealed that overexpression of miRNA-96-5p substantially reduced FOXO3 protein expression. We used the GEPIA, UALCAN and KM-plotter databases to investigate the expression of FOXO3 in human breast cancer and adjacent normal tissues, and its correlation with survival. In addition, we found that FOXO3 spoiled miR-96-5p induced breast cancer cell proliferation block effecting.

Conclusions: miRNA-96-5p may exert a tumor promotion role through negatively regulating tumor suppressor gene FOXO3 and promoting cell proliferation.

Keywords: Breast cancer; FOXO3; miRNA-96-5p; proliferation.