miR-125a-5p reverses epithelial-mesenchymal transition and restores drug sensitivity by negatively regulating TAFAZZIN signaling in breast cancer

Abstract

MicroRNA (miR)-125a-5p represses tafazzin phospholipid-lysophospholipid transacylases (TAFAZZIN ) expression and inhibits the epithelial-mesenchymal transition (EMT) of ovarian cancer cells. EMT was found to have a crucial role in the acquisition of chemoresistance. Thus, the present study aimed to determine whether miR-125a-5p reverses EMT and restores drug sensitivity by negatively regulating TAFAZZIN in breast cancer. The expression of miR-125a-5p/TAFAZZIN and its association with chemotherapy response were determined in tissue samples from patients with breast cancer. Furthermore, the effects of miR-125a-5p on breast cancer cells were elucidated using cell proliferation and cell apoptosis assays. Then, the regulatory mechanism of miR-125a-5p in breast cancer was investigated by reverse transcription-quantitative PCR , western blotting, dual-luciferase reporter and RNA immunoprecipitation assays. The results demonstrated that miR-125a-5p inhibited the EMT of MCF-7/adriamycin (Adr) breast cancer cells, as well as decreased the proliferation and increased the apoptosis of breast cancer cells treated with Adr/docetaxel. In addition, miR-125a-5p downregulated the expression levels of TAFAZZIN , Transglutaminase 2, phosphorylated-AKT, N-cadherin, vimentin and proliferating cell nuclear antigen, and significantly increased those of E-cadherin, cleaved caspase-3 and Bax in MCF7/Adr cells. Similar results were obtained with small interfering RNA -TAFAZZIN . Moreover, TAFAZZIN was identified as a direct target of miR-125a-5p in MCF7/Adr breast cancer cells. In addition, increased miR-125a-5p expression was observed in breast tumors from patients exhibiting a chemotherapy response, and TAFAZZIN mRNA expression was elevated in patients with no chemotherapy response. Hence, miR-125a-5p expression was negatively correlated with TAFAZZIN mRNA expression in breast cancer tissues. All these data suggested that miR-125a-5p reverses EMT and restores drug sensitivity by negatively regulating TAFAZZIN in breast cancer and, therefore, has potential as a novel therapeutic target for this disease.