MicroRNA-452 contributes to the docetaxel resistance of breast cancer cells

作者：Hu, Qing; Chen, Wei-xian; Zhong, Shan-liang; Zhang, Jun-ying; Ma, Teng-fei; Ji, Hao; Lv, Meng-meng; Tang, Jin-hai^*; Zhao, Jian-hua

来源：Tumor Biology, 2014, 35(7): 6327-6334.

DOI：10.1007/s13277-014-1834-z

• Breast cancer
• MiRNA-452
• Docetaxel
• APC4
• Resistance

MicroRNA-452 (miRNA-452) was overexpressed in docetaxel-resistant human breast cancer MCF-7 cells (MCF-7/DOC). However, its role in modulating the sensitivity of breast cancer cells to docetaxel (DOC) remains unclear. The aim of this study is to investigate the role of miRNA-452 in the sensitivity of breast cancer cells to DOC.
Real-time quantitative PCR (RT-qPCR) were used to identify the differential expression of miRNA-452 between MCF-7/DOC and MCF-7 cells. MiRNA-452 mimic was transfected into MCF-7 cells and miRNA-452 inhibitor was transfected into MCF-7/DOC cells. The role of miRNA-452 in these transfected cells was evaluated using RT-qPCR, MTT assay, and flow cytometry assay. The relationship of miRNA-452 and its predictive target gene "anaphase-promoting complex 4" (APC4) was analyzed by RT-qPCR and Western blot.
MiRNA-452 showed significantly higher expression (78.9-folds) in MCF-7/DOC cells compared to parental MCF-7 cells. The expression of miRNA-452 in the mimic transfected MCF-7 cells was upregulated 212.2-folds (P < 0.05) compared to its negative control (NC), and the half maximal inhibitory concentration (IC50) value of DOC (1.98 +/- 0.15 mu M) was significantly higher than that in its NC (0.85 +/- 0.08 mu M, P < 0.05) or blank control (1.01 +/- 0.19 mu M, P < 0.05). Furthermore, its apoptotic rate (6.3 +/- 1.3 %) was distinctly decreased compared with that in its NC (23.8 +/- 6.6 %, P < 0.05) or blank control (18.6 +/- 4.7 %, P < 0.05). In contrast, the expression of miRNA-452 in the inhibitor-transfected MCF-7/DOC cells was downregulated 0.58-fold (P < 0.05) compared to its NC, the IC50 value of DOC (44.5 +/- 3.2 mu M) was significantly lower than that in its NC (107.3 +/- 6.63 mu M, P < 0.05) or blank control (102.22 +/- 11.34 mu M, P < 0.05), and the apoptotic rate (45.5 +/- 10.8 %) was distinctly increased compared with its NC (9.9 +/- 2.2 %, P < 0.05) and blank control (9.4 +/- 2.5 %, P < 0.05). Further, there was an inverse association between miRNA-452 and APC4 expression in breast cancer cells in vitro.
Dysregulation of miRNA-452 involved in the DOC resistance formation of breast cancer cells may be, in part, via targeting APC4.

• 出版日期2014-7
• 单位徐州医科大学