miR-223-3p Targets KIF4A and Promotes the Oxidative Stress-Mediated Apoptosis of Breast Cancer Cells.

Abstract

Background: The abnormal expression of kinase family member 4A (KIF4A) is linked to breast cancer progression, with numerous miRNAs exhibiting abnormal expression. Thus, there is an urgent need to investigate the mechanisms of action of miRNAs and their target genes for the diagnosis and treatment of breast cancer. Materials and Methods: A bioinformatics analysis was conducted to screen for KIF4A, a key gene involved in oxidative stress in breast cancer cells. Using CCK8, EdU, cell healing, and Transwell assays, the knockdown of KIF4A was found to effectively inhibit the proliferation, migration, and invasion of breast cancer cells. Dual-luciferase assay and Western blotting confirmed that miR-223-3p targets and regulates KIF4A expression. The impact of miR-223-3p and KIF4A on oxidative stress in breast cancer cells was assessed through reactive oxygen species (ROS), superoxide dismutase (SOD), and malondialdehyde (MDA) measurements. Flow cytometry was used to evaluate tumor cell apoptosis. Results: Our results suggest that KIF4A is a downstream target of miR-223-3p. miR-223-3p inhibits the proliferation and invasion of breast cancer cells by directly targeting and downregulating KIF4A. Importantly, we found that miR-223-3p and KIF4A play important roles in regulating oxidative stress and apoptosis in breast cancer cells. Specifically, miR-223-3p promoted apoptosis by inhibiting the expression of KIF4A, increasing the accumulation level of ROS and MDA, and inhibiting the activity of SOD while KIF4A was overexpressed.