miR-27a regulates the sensitivity of breast cancer cells to cisplatin treatment via BAK-SMAC/DIABLO-XIAP axis
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MicroRNA-27a (miR-27a) has been reported to be an onco-microRNA in multiple cancers promoting tumor growth and metastasis, but the role of miR-27a in regulating the cancer sensitivity to chemotherapy remains unknown. In this study, upregulation of miR-27a was validated by real-time PCR analysis in breast cancer (BC) cell lines and samples of BC patients. A negative correlation between miR-27a and bak was also observed in normal breast epithelial cell line MCF-10A and BC cell lines, suggesting that the bak is the potential target of miR-27a. miR-27a could modulate the growth and metastasis of BC cells. More importantly, we found that knockdown of miR-27a by the specific inhibitors significantly increased the sensitivity of T-47D cells to cisplatin (CDDP) treatment. After further investigation, we indicated that the knockdown of miR-27a promoted the apoptosis via mitochondrial pathway in T-47D cells treated with CDDP, depending on the BAK-second mitochondria-derived activator of caspase/direct IAP binding protein with low pI (SMAC/DIABLO)-X-linked inhibitor of apoptosis (XIAP) axis. Interestingly, we found that the sensitivity of T-47D cells to some other chemotherapeutic agents (5-fluorouracil, doxorubicin, and tumor necrosis factor-related apoptosis-inducing ligand) was also regulated by miR-27a. These findings improve our understanding of the role of miR-27a in breast cancer and might provide a novel strategy for cancer therapy.
KeywordsBreast cancer Cisplatin miR-27a BAK SMAC/DIABLO XIAP
Thanks are due to Central Laboratory of The First Affiliated Hospital of Wenzhou Medical University for supporting this study
XZ designed the study. SZ and XZ wrote the manuscript. SZ, QH, and KL measured the sensitivity of tumor cells and the related statistical analysis. SZ and JY carried out the cell culture and transfection, Western blot, RT-PCR, and flow cytometry. All authors approved the final version of the manuscript.
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Conflicts of interest
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