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

  • Research Article
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Tumor Biology

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Abstract

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 μM) was significantly higher than that in its NC (0.85 ± 0.08 μM, P < 0.05) or blank control (1.01 ± 0.19 μM, 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 μM) was significantly lower than that in its NC (107.3 ± 6.63 μM, P < 0.05) or blank control (102.22 ± 11.34 μM, 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.

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Acknowledgments

This study was supported by grants from the National Natural Science Foundation of China (No. 81272470).

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Authors and Affiliations

  1. Department of General Surgery, Xuzhou Medical College, Xuzhou, 221004, China

    Qing Hu & Hao Ji

  2. Department of General Surgery, Jiangsu Cancer Hospital, Nanjing, 210009, China

    Wei-xian Chen, Meng-meng Lv & Jin-hai Tang

  3. Clinical Laboratory Center, Jiangsu Cancer Hospital, Nanjing, 210009, China

    Shan-liang Zhong, Teng-fei Ma & Jian-hua Zhao

  4. Department of Oncology, Xuzhou Medical College, Xuzhou, 221004, China

    Jun-ying Zhang

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  1. Qing Hu
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  2. Wei-xian Chen
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  8. Jin-hai Tang
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Corresponding authors

Correspondence to Jin-hai Tang or Jian-hua Zhao.

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Hu, Q., Chen, Wx., Zhong, Sl. et al. MicroRNA-452 contributes to the docetaxel resistance of breast cancer cells. Tumor Biol. 35, 6327–6334 (2014). https://doi.org/10.1007/s13277-014-1834-z

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  • DOI: https://doi.org/10.1007/s13277-014-1834-z

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