Abstract
OBJECTIVE: MicroRNAs (miRNAs) have been confirmed to play an essential role in modulating cancer cell proliferation, metastasis, and sensitivity to chemotherapy. However, the correlation between miR-132-3p expression and etoposide (VP16) induced apoptosis in human breast cancer cells remains poorly understood. METHODS: Six datasets, including three gene expression profile datasets and three microRNA (miRNA) expression profile datasets, were downloaded from the NCBI Gene Expression Omnibus (GEO) database to identify miR-132-3p and GSK3B expression in breast cancer. Kaplan-Meier and log-rank testing were performed to evaluate the effect of miR-132-3p and GSK3B on the survival of breast cancer. Flow cytometry analysis was used to determine the effects of miR-132-3p and GSK3B on breast cancer cell apoptosis. Luciferase reporter assay, Western blot, and real-time PCR were used to determine the regulatory effect of miR-132-3p on GSK3B. RESULTS: miR-132-3p was significantly downregulated in breast cancer tissues compared with normal breast epithelial cells, whereas GSK3B expression was remarkably over-expressed in breast cancer tissues. The patients with low miR-132-3p or high GSK3B expression had worse overall survival. Luciferase reporter assay, Western blot, and real-time PCR confirmed that miR-132-3p could inhibit GSK3B protein and mRNA expression via binding to the 3’-UTR of GSK3B. Furthermore, miR-132-3p enhanced VP16-induced breast cancer cell apoptosis through targeting GSK3B. CONCLUSION: Collectively, the results of this study indicated that miR-132-3p was downregulated in breast cancer tissues and directly targeted GSK3B to be implicated in the modulation of breast cancer cell apoptosis, suggesting that miR-132-3p/GSK3B might be a novel, effective therapeutic target for treating patients with breast cancer.