文章：

miR-182通过靶向乳腺癌细胞中的MET调节曲妥珠单抗耐药

miR-182 regulates trastuzumab resistance by targeting MET in breast cancer cells 

原文发布日期：2018-06-21 

英文摘要：

It has been found that microRNAs (miRNAs) play a key role in drug resistance. The purpose of the current study was to investigate the function of miR-182 in trastuzumab resistance in breast cancer cells. The results showed that both breast cancer SKBR3 trastuzumab-resistant cells (SKBR3/TR) and BT474 trastuzumab-resistant cells (BT474/TR) were associated with miR-182 downregulation compared with their parental cells. Ectopic expression of the miR-182 mimic inhibited trastuzumab resistance, decreasing the invasion and migration of these trastuzumab-resistant cells. However, the miR-182 inhibitor increased trastuzumab resistance, cell invasion, and migration in the parental cells. In addition, MET is a directly targeted gene of miR-182 in breast cancer cells. MET knockdown showed an inhibitory effect of trastuzumab resistance on trastuzumab-resistant cells. In contrast, MET overexpression in SKBR3 cells produced an effect that promotes resistance to trastuzumab. Moreover, we revealed that overexpression of miR-182 reduced trastuzumab resistance in trastuzumab-resistant cells due in part to MET/PI3K/AKT/mTOR signaling pathway inactivation. Furthermore, miR-182 could also sensitize SKBR3/TR cells to trastuzumab in vivo. In conclusion, our results suggest that the activation of miR-182 or inactivation of its target gene pathway could be used as a new method to reverse trastuzumab resistance in breast cancer. 

摘要翻译： 

研究发现，微小核糖核酸（miRNA）在耐药性形成中起关键作用。本研究旨在探讨miR-182在乳腺癌细胞曲妥珠单抗耐药性中的功能。结果显示：与亲代细胞相比，乳腺癌SKBR3曲妥珠单抗耐药细胞（SKBR3/TR）和BT474曲妥珠单抗耐药细胞（BT474/TR）均出现miR-182下调现象。外源性导入miR-182模拟物可通过降低耐药细胞的侵袭和迁移能力，从而抑制曲妥珠单抗耐药性；而miR-182抑制剂则会增强亲代细胞对曲妥珠单抗的耐药性及细胞侵袭迁移能力。此外，MET是miR-182在乳腺癌细胞中的直接靶基因——敲低MET基因可抑制曲妥珠单抗耐药细胞的耐药性，反之在SKBR3细胞中过表达MET则会促进曲妥珠单抗耐药。我们进一步发现，miR-182过表达能部分通过抑制MET/PI3K/AKT/mTOR信号通路来降低耐药细胞对曲妥珠单抗的耐药性。更重要的是，体内实验证实miR-182能增强SKBR3/TR细胞对曲妥珠单抗的敏感性。综上所述，激活miR-182或抑制其靶基因信号通路可作为逆转乳腺癌曲妥珠单抗耐药的新策略。

原文链接：

miR-182 regulates trastuzumab resistance by targeting MET in breast cancer cells