miR-503-3p promotes epithelialemesenchymal transition in breast cancer by directly targeting SMAD2 and E-cadherin
miR-503-3p promotes epithelialemesenchymal transition in breast cancer by directly targeting SMAD2 and E-cadherin
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miR-503-3p通过直接靶向SMAD2和E-钙粘蛋白促进乳腺癌上皮间质转化
DOI：
10.1016/j.jgg.2016.10.005
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发表时间：
2017-02-20
影响因子：
5.9
通讯作者：
Song, Yongmei
中科院分区：
文献类型：
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作者：
Zhao, Zitong;Fan, Xinyi;Song, Yongmei
虽然在临床和基础研究的进展显着增加了我们对乳腺癌的理解，很少有人知道乳腺癌转移的分子机制。因此，寻找有效的治疗靶点来预防乳腺癌转移是当前迫切需要解决的问题。miR-503- 3 p在其他癌症中的功能已经研究过，但其在乳腺癌中的作用仍不明确。在这里，我们发现miR-503- 3 p在乳腺癌组织和血浆中过表达，与邻近的正常乳腺组织和健康个体的血浆相比。此外，我们确定miR-503- 3 p是乳腺癌细胞增殖、迁移和侵袭的癌基因。miR-503- 3 p在乳腺癌细胞中的上调通过直接结合其mRNA 30非翻译区来抑制上皮间质转化（EMT）相关蛋白SMAD 2和上皮标志蛋白E-cadherin的表达，而增加间质标志蛋白包括波形蛋白和N-cadherin的表达。总之，我们的研究结果支持miR-503- 3 p在诱导乳腺癌EMT中的关键作用，并表明血浆miR-503- 3 p可能是乳腺癌的有用诊断生物标志物。中国科学院遗传与发育生物学研究所、中国遗传学会版权所有（C）2016由爱思唯尔有限公司和科学出版社出版。All rights reserved.
Although progress in clinical and basic research has significantly increased our understanding of breast cancer, little is known about the molecular mechanism underlying breast cancer metastasis. Identification of effective therapeutic targets to prevent breast cancer metastasis is urgently needed. The function of miR-503-3p has been investigated in other cancers, but its role in breast cancer remains undefined. Here, we found that miR-503-3p was overexpressed in breast cancer tissue and plasma compared with adjacent normal breast tissue and with plasma from healthy individuals. Moreover, we identified miR-503-3p to be an oncogene of breast cancer cell proliferation, migration and invasion. Upregulation of miR-503-3p in breast cancer cells inhibited expression of epithelialemesenchymal transition (EMT)related protein SMAD2 and the epithelial marker protein E-cadherin by directly binding to their mRNA 30 untranslated region, whereas increased expression of mesenchymal marker proteins, including vimentin and N-cadherin. Taken together, our findings support a critical role for miR-503-3p in induction of breast cancer EMT and suggest that plasma miR-503-3p may be a useful diagnostic biomarker for breast cancer. Copyright (C) 2016, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, and Genetics Society of China. Published by Elsevier Limited and Science Press. All rights reserved.