title: MicroRNA-452 contributes to the docetaxel resistance of breast cancer cells.
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.
authors.affiliation: Department of General Surgery, Xuzhou Medical College, Xuzhou, 221004, China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Hu
authors.forename: Wei-xian
authors.initials: WX
authors.lastname: Chen
authors.forename: Shan-liang
authors.initials: SL
authors.lastname: Zhong
authors.forename: Jun-ying
authors.initials: JY
authors.lastname: Zhang
authors.forename: Teng-fei
authors.initials: TF
authors.lastname: Ma
authors.forename: Hao
authors.initials: H
authors.lastname: Ji
authors.forename: Meng-meng
authors.initials: MM
authors.lastname: Lv
authors.forename: Jin-hai
authors.initials: JH
authors.lastname: Tang
authors.forename: Jian-hua
authors.initials: JH
authors.lastname: Zhao
mesh_terms: D064192:Apc4 Subunit, Anaphase-Promoting Complex-Cyclosome / Q000235:genetics; D017209:Apoptosis / Q000187:drug effects; D001943:Breast Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D049109:Cell Proliferation / Q000187:drug effects; D000077143:Docetaxel; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D061986:MCF-7 Cells; D035683:MicroRNAs / Q000096:biosynthesis / Q000235:genetics*; D043823:Taxoids / Q000008:administration & dosage
chemical_list: C577369:ANAPC4 protein, human; D064192:Apc4 Subunit, Anaphase-Promoting Complex-Cyclosome; C574051:MIRN452 microRNA, human; D035683:MicroRNAs; D043823:Taxoids; D000077143:Docetaxel