Regulation of miR-19 to Breast Cancer Chemoresistance Through Targeting PTEN (Publication with Expression of Concern)
Regulation of miR-19 to Breast Cancer Chemoresistance Through Targeting PTEN (Publication with Expression of Concern)
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DOI：
10.1007/s11095-011-0570-y
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发表时间：
2011-12-01
影响因子：
3.7
通讯作者：
Shim, Hyunsuk
中科院分区：
文献类型：
--
作者：
Liang, Zhongxing;Li, Yuhua;Shim, Hyunsuk
为了探讨 miR-19 是否参与多药耐药性 (MDR)（乳腺癌死亡的主要原因之一）的调节，并调节肿瘤细胞对化疗药物的敏感性。我们使用 miRNA 微阵列分析了三种 MDR 细胞系中的 miRNA 表达水平，并与其亲代细胞系 MCF-7 进行比较。我们在体外和体内研究了 miR-19 抑制剂是否使 MDR 细胞对化疗药物敏感。与亲代细胞系 MCF-7 相比，MiR-19 在所有三种 MDR 细胞系中均过表达。 MDR细胞中miR-19的表达水平与PTEN的表达水平呈负相关。 miR-19a 抑制剂可恢复 MDR 细胞对细胞毒性药物的敏感性；给予 LNA-antimiR-19a（一种化学修饰的 miR-19a 抑制剂）可在体内使 MDR 细胞对化疗药物敏感。我们的研究结果首次证明 miR-19 通过调节 PTEN 参与多药耐药性，并表明 miR-19 可能是预防和逆转肿瘤细胞 MDR 的潜在靶点。
To explore whether miR-19 is involved in the regulation of multidrug resistance (MDR), one of the main causes of breast cancer mortality, and modulates sensitivity of tumor cells to chemotherapeutic agents.We analyzed miRNA expression levels in three MDR cell lines in comparison with their parent cell line, MCF-7, using a miRNA microarray. We investigated whether inhibitor of miR-19 sensitized MDR cells to chemotherapeutic agents in vitro and in vivo.MiR-19 was overexpressed in all three MDR cell lines compared to their parental cell line, MCF-7. Expression levels of miR-19 in MDR cells were inversely consistent with those of PTEN. Inhibitor of miR-19a restored sensitivity of MDR cells to cytotoxic agents; administration of LNA-antimiR-19a, a chemo-modified miR-19a inhibitor, sensitized MDR cells to chemotherapeutic agents in vivo.Our findings demonstrate, for the first time, involvement of miR-19 in multidrug resistance through modulation of PTEN and suggest that miR-19 may be a potential target for preventing and reversing MDR in tumor cells.