文章：

MicroRNA-140-5p通过靶向VEGF-A抑制乳腺癌的侵袭和血管生成

MicroRNA-140-5p inhibits invasion and angiogenesis through targeting VEGF-A in breast cancer

原文发布日期：2017-07-28 

英文摘要：

MicroRNAs (miRNAs) have been proven to be involved in cell metastasis and angiogenesis by interaction with the target mRNAs. Evidence has been confirmed that miR-140-5p is a tumor suppressor in human cancers such as breast cancer. However, the potential molecular mechanism of miR-140-5p in breast cancer invasion and angiogenesis is still poorly understood. According to our study, we reported that miR-140-5p inhibited the tumor invasion and angiogenesis of breast cancer cells both in vitro and in vivo by targeting VEGF-A. The mRNA amount of miR-140-5p was decreased in the breast cancer clinical samples and breast cancer with metastasis compared with the corresponding adjacent normal tissues and cancer without metastasis. MiR-140-5p mimics and a negative control were transfected into human MCF-7 and MDA-MB-231 cells. Transwell chambers were used to detect the invasive ability of the cells, and the angiogenic ability was assessed by tube-formation assay. The markers of invasion and angiogenesis, VEGF-A, CD31 and MMP-9, were detected by using immunohistochemistry and western blot analysis in vivo. VEGF-A was verified as a possible target gene of miR-140-5p, and corroborated by dual-luciferase reporter and ELISA. Taken together, the study elucidates the molecular mechanisms by which miR-140-5p inhibits breast cancer metastasis and angiogenesis, and provides a potent evidence for the development of a novel microRNA-targeting anticancer strategy for breast cancer patients. 

摘要翻译： 

MicroRNAs（miRNAs）已被证实通过与其靶向mRNAs的相互作用参与细胞转移和血管生成过程。现有证据表明，miR-140-5p在乳腺癌等多种人类癌症中具有肿瘤抑制功能。然而，miR-140-5p在乳腺癌侵袭和血管生成中的潜在分子机制尚不明确。本研究通过实验证实：miR-140-5p通过靶向VEGF-A，在体外和体内实验中均能抑制乳腺癌细胞的肿瘤侵袭和血管生成。在乳腺癌临床样本及发生转移的乳腺癌组织中，miR-140-5p的mRNA表达量较对应癌旁正常组织及未转移癌组织显著降低。我们将miR-140-5p模拟物和阴性对照分别转染至人MCF-7和MDA-MB-231细胞系，采用Transwell小室检测细胞侵袭能力，并通过血管形成实验评估血管生成能力。在体内实验中，通过免疫组化和蛋白质印迹法检测了侵袭与血管生成标志物VEGF-A、CD31及MMP-9的表达水平。双荧光素酶报告基因实验和ELISA检测共同验证VEGF-A是miR-140-5p的潜在靶基因。本研究系统阐明了miR-140-5p抑制乳腺癌转移和血管生成的分子机制，为开发针对乳腺癌患者的microRNA靶向抗癌策略提供了有力依据。

原文链接：

MicroRNA-140-5p inhibits invasion and angiogenesis through targeting VEGF-A in breast cancer