MiR-181a enhances drug sensitivity in mitoxantone-resistant breast cancer cells by targeting breast cancer resistance protein (BCRP/ABCG2)
MiR-181a enhances drug sensitivity in mitoxantone-resistant breast cancer cells by targeting breast cancer resistance protein (BCRP/ABCG2)
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MiR-181a 通过靶向乳腺癌耐药蛋白 (BCRP/ABCG2) 增强米托吨酮耐药乳腺癌细胞的药物敏感性
DOI：
10.1007/s10549-013-2607-x
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发表时间：
2013-06-01
影响因子：
3.8
通讯作者：
Wei, Minjie
中科院分区：
文献类型：
--
作者：
Jiao, Xuyang;Zhao, Lin;Wei, Minjie
乳腺癌耐药蛋白 (BCRP)/ATP 结合盒亚家族 G 成员 2 (ABCG2) 介导乳腺癌的多药耐药性 (MDR)。在本研究中，我们旨在研究 microRNA 在调节乳腺癌细胞 BCRP 表达和 BCRP 介导的耐药性中的作用。进行微阵列分析以确定 MX 耐药乳腺癌细胞系 MCF-7/MX 及其亲代 MX 敏感细胞系 MCF-7 之间靶向 BCRP 的 miRNA 的差异表达模式。研究发现 MiR-181a 是 MCF-7/MX 细胞中下调最显着的 miRNA。荧光素酶活性测定表明，miR-181a 模拟物通过靶向 BCRP mRNA 的 3' 非翻译区 (UTR) 抑制 BCRP 表达。 miR-181a 的过度表达下调 BCRP 表达，并使 MX 耐药 MCF-7/MX 细胞对 MX 敏感。在裸鼠异种移植模型中，瘤内注射 miR-181a 模拟物抑制 BCRP 表达，并增强 MX 的抗肿瘤活性。此外，miR-181a抑制剂上调BCRP表达，并使MX敏感的MCF-7细胞对MX产生抗性。这些发现表明 miR-181a 通过与 BCRP mRNA 的 3'-UTR 结合来调节 BCRP 表达。 MiR-181a 对于调节 BCRP 介导的 MX 耐药性至关重要。 MiR-181a可能是预防和逆转乳腺癌耐药性的潜在靶点。
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.