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Breast cancer resistance protein (BCRP)/ATP-binding cassette subfamily G member 2 (ABCG2) mediates multidrug resistance (MDR) in breast cancers. In this study, we aimed to investigate the role of microRNAs in regulation of BCRP expression and BCRP-mediated drug resistance in breast cancer cells. Microarray analysis was performed to determine the differential expression patterns of miRNAs that target BCRP between the MX-resistant breast cancer cell line MCF-7/MX and its parental MX-sensitive cell line MCF-7. MiR-181a was found to be the most significantly down-regulated miRNA in MCF-7/MX cells. Luciferase activity assay showed that miR-181a mimics inhibited BCRP expression by targeting the 3' untranslated region (UTR) of the BCRP mRNA. Overexpression of miR-181a down-regulated BCRP expression, and sensitized MX-resistant MCF-7/MX cells to MX. In a nude mouse xenograft model, intratumoral injection of miR-181a mimics inhibited BCRP expression, and enhanced the antitumor activity of MX. In addition, miR-181a inhibitors up-regulated BCRP expression, and rendered MX-sensitive MCF-7 cells resistant to MX. These findings suggest that miR-181a regulates BCRP expression via binding to the 3'-UTR of BCRP mRNA. MiR-181a is critical for regulation of BCRP-mediated resistance to MX. MiR-181a may be a potential target for preventing and reversing drug resistance in breast cancer.

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Breast cancer is the most common type of cancer among women worldwide, and the incidence of breast cancer is increasing in the developing world. Estrogen exposure is a major risk factor for breast cancer, and estrogen oxidative metabolites have been implicated in chemical carcinogenesis. Xeroderma pigmentosum complementary group C (XPC) plays an important and multifaceted role in cell protection from oxidative DNA damage. Thus, XPC inactivation may be involved in the early stage of breast cancer. The aim of this study was to investigate the expression of XPC protein in sporadic breast cancer tissues and determine whether XPC expression influences breast cancer malignancy and clinical outcome. Fifteen cases of adjacent non-tumor breast tissue, 28 cases of fibroadenomas and 235 cases of breast carcinomas were examined by immunohistochemistry using polyclonal antibody to XPC. Both cytoplasmic and nuclear expression level of XPC were downregulated in breast carcinoma when compared to non-tumor tissues (P < 0.05). The nuclear expression level of XPC was significantly associated with expression of BCL2 (r = 0.231, P = 0.033) and p53 (r = 0.205, P = 0.011), and nuclear expression of XPC was significantly associated with patients' age (P = 0.024). Neither cytoplasmic nor nuclear expression level of XPC had impact on patients' survival in the whole samples. However, XPC expression was correlated with adverse survival in HER2-positive, but not HER2-negative, tumors, as demonstrated by Kaplan-Meier analysis. Our results suggested that the XPC protein is involved in the occurrence and progression of breast cancer.