MiR-199a-3p enhances breast cancer cell sensitivity to cisplatin by downregulating TFAM (TFAM).

Abstract

Chemotherapy resistance is the major obstacle to the effective therapy of cancer. While the mechanism of chemotherapy resistance is still not fully understood. Increasing evidences demonstrated that microRNAs (miRNAs) may have a crucial function in chemotherapy resistance through modulating intracellular pathways. MiR-199a has been shown to be involved in multiple malignancy-related processes, although the precise mechanism is unclear at present. In this study, we found that the expression level of miR-199a-3p was lower in cisplatin (DDP) resistant breast cancer MDA-MB-231/DDP cells compared with parental DDP-sensitive cells. Inhibition of miR-199a-3p in MDA-MB-231 cells significantly attenuated DDP-induced apoptosis and anti-proliferative effects, while overexpression of miR-199a-3p in MDA-MB-231/DDP cells increased the sensitivity to DDP. Moreover, expression levels of mitochondrial transcription factor A (TFAM) were modulated by miR-199a-3p. The luciferase reporter assay indicated that TFAM may be the target gene of miR-199a. Knocking down of TFAM could partially reverse DDP resistance in MDA-MB-231 cells induced by miR-199a-3p inhibition, while TFAM overexpression could partially restore miR-199a-3p-induced chemo-sensitivity of MDA-MB-231/DDP cells to DDP. These results show that miR-199a-3p is able to attenuate cisplatin resistance in breast cancer cells through inhibiting TFAM expression.