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Tumour Biol. 2016 May;37(5):6837-45. doi: 10.1007/s13277-015-4500-1. Epub 2015 Dec 10.

miR-27a regulates the sensitivity of breast cancer cells to cisplatin treatment via BAK-SMAC/DIABLO-XIAP axis.

Author information

1
Surgical Oncology Department, The First Affiliated Hospital of Wenzhou Medical University, Nanbaixiang Town, Ouhai District, Wenzhou City, Zhejiang Province, 325000, China.
2
Surgical Oncology Department, The First Affiliated Hospital of Wenzhou Medical University, Nanbaixiang Town, Ouhai District, Wenzhou City, Zhejiang Province, 325000, China. zjzxh1974@126.com.

Abstract

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.

KEYWORDS:

BAK; Breast cancer; Cisplatin; SMAC/DIABLO; XIAP; miR-27a

PMID:
26662313
DOI:
10.1007/s13277-015-4500-1
[Indexed for MEDLINE]

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