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.
Breast cancer MiRNA-452 Docetaxel APC4 Resistance
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This study was supported by grants from the National Natural Science Foundation of China (No. 81272470).
Zhu Y, Wang A, Liu MC, Zwart A, Lee RY, Gallagher A, et al. Estrogen receptor alpha positive breast tumors and breast cancer cell lines share similarities in their transcriptome data structures. International Journal Oncology. 2006;29:1581–9.Google Scholar
Tian W, Chen J, He H, Deng Y. MicroRNAs and drug resistance of breast cancer: basic evidence and clinical applications. Clinical & translational oncology: official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico. 2013;15:335–42.CrossRefGoogle Scholar
Liu SG, Qin XG, Zhao BS, Qi B, Yao WJ, Wang TY, et al. Differential expression of miRNAs in esophageal cancer tissue. Oncology letters. 2013;5:1639–42.PubMedCentralPubMedGoogle Scholar
Puerta-Gil P, Garcia-Baquero R, Jia AY, Ocana S, Alvarez-Mugica M, Alvarez-Ossorio JL, et al. Mir-143, mir-222, and mir-452 are useful as tumor stratification and noninvasive diagnostic biomarkers for bladder cancer. The American Journal Pathology. 2012;180:1808–15.CrossRefGoogle Scholar
Liu C, Kelnar K, Vlassov AV, Brown D, Wang J, Tang DG. Distinct microRNA expression profiles in prostate cancer stem/progenitor cells and tumor-suppressive functions of let-7. Cancer Res. 2012;72:3393–404.CrossRefPubMedGoogle Scholar
Sheehy NT, Cordes KR, White MP, Ivey KN, Srivastava D. The neural crest-enriched microRNA mir-452 regulates epithelial–mesenchymal signaling in the first pharyngeal arch. Development (Cambridge, England). 2010;137:4307–16.PubMedCentralCrossRefGoogle Scholar
Gokhale A, Kunder R, Goel A, Sarin R, Moiyadi A, Shenoy A, et al. Distinctive microRNA signature of medulloblastomas associated with the Wnt signaling pathway. Journal of Cancer Research and Therapeutics. 2010;6:521–9.CrossRefPubMedGoogle Scholar
Kastl L, Brown I, Schofield AC. MiRNA-34a is associated with docetaxel resistance in human breast cancer cells. Breast Cancer Research and Treatment. 2012;131:445–54.CrossRefPubMedGoogle Scholar
Shen DY, Zhang W, Zeng X, Liu CQ. Inhibition of Wnt/beta-catenin signaling downregulates p-glycoprotein and reverses multi-drug resistance of cholangiocarcinoma. Cancer Sci. 2013;104:1303–8.CrossRefPubMedGoogle Scholar
Dikovskaya D, Schiffmann D, Newton IP, Oakley A, Kroboth K, Sansom O, et al. Loss of APC induces polyploidy as a result of a combination of defects in mitosis and apoptosis. The Journal of Cell Biology. 2007;176:183–95.PubMedCentralCrossRefPubMedGoogle Scholar