Glabridin attenuates the migratory and invasive capacity of breast cancer cells by activating microRNA-200c.

Glabridin attenuates the migratory and invasive capacity of breast cancer cells by activating microRNA-200c.
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DOI:
10.1111/cas.12426
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发表时间:
2014-07
期刊:
影响因子:
5.7
通讯作者:
Li Z
Li Z
中科院分区:
医学2区
文献类型:
--
作者:
Ye X;Jiang F;Li Y;Mu J;Si L;Wang X;Ning S;Li Z

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乳腺癌是人类女性常见的一种恶性肿瘤,目前的治疗方法并不令人满意,因为转移率很高。GLA通过FAK/ROS信号通路发挥作用,已被用作抗氧化剂和抗肿瘤转移药物。然而,关于microRNA(MiRNA)对GLA抗转移活性的影响,人们知之甚少。MiRNA-200家族在三阴性乳腺癌中经常低水平表达,通过阻断上皮-间充质转化来抑制转移。在这里,我们发现GLA通过激活miR-200C来减弱乳腺癌细胞的迁移和侵袭能力。GLA在体外和体内诱导间充质-上皮转化,其结果是上皮标记物E-钙粘附素表达增加,而间质标记物波形蛋白表达降低。MiR-200C过表达使E-钙粘蛋白表达增强,波形蛋白表达降低。此外,在暴露于GLA的MDA-MB-231和BT-549乳腺癌细胞中,miR-200C的敲除阻断了GLA诱导的间质-上皮转化,并减轻了GLA诱导的迁移和侵袭的抑制。因此,GLA上调miR-200C对于乳腺癌患者的抗转移治疗具有相当大的治疗潜力。
Current treatments for breast cancer, a common malignancy in human females, are less than satisfactory because of high rates of metastasis. Glabridin (GLA), which acts through the FAK/ROS signaling pathway, has been used as an antioxidant and anti-metastatic agent. However, little is known regarding the effect of microRNA (miRNA) on GLA's anti-metastatic activity. The miRNA-200 family, which is frequently expressed at low levels in triple negative breast cancers, inhibits metastasis by blocking the epithelial–mesenchymal transition. Here, we found that GLA attenuated the migratory and invasive capacity of breast cancer cells by activating miR-200c. GLA induced the mesenchymal–epithelial transition in vitro and in vivo, as determined by increased expression of the epithelial marker, E-cadherin, and decreased expression of the mesenchymal marker, vimentin. Overexpression of miR-200c enhanced the expression of E-cadherin and decreased the expression of vimentin. Furthermore, in MDA-MB-231 and BT-549 breast cancer cells exposed to GLA, knockdown of miR-200c blocked the GLA-induced mesenchymal–epithelial transition and alleviated the GLA-induced inhibition of migration and invasion. Thus, elevation of miR-200c by GLA has considerable therapeutic potential for anti-metastatic therapy for breast cancer patients.
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