Teaching Laboratory of Morphology, Dalian Medical University, Dalian, China.
Key Laboratory of Tumor Stem Cell Research of Liaoning Province, Dalian Medical University, Dalian, China.
Cancer Gene Ther. 2017 Sep;24(9):386-392. doi: 10.1038/cgt.2017.30. Epub 2017 Jul 28.
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.
微小 RNA（miRNAs）已被证明通过与靶 mRNAs 的相互作用参与细胞转移和血管生成。有证据证实，miR-140-5p 是人类癌症（如乳腺癌）中的肿瘤抑制因子。然而，miR-140-5p 在乳腺癌侵袭和血管生成中的潜在分子机制仍知之甚少。根据我们的研究，我们报道 miR-140-5p 通过靶向 VEGF-A 抑制乳腺癌细胞的肿瘤侵袭和血管生成。与相应的相邻正常组织和无转移的癌症相比，乳腺癌临床样本和转移的乳腺癌中 miR-140-5p 的 mRNA 量降低。将 miR-140-5p 模拟物和阴性对照转染入人 MCF-7 和 MDA-MB-231 细胞中。Transwell 室用于检测细胞的侵袭能力，通过管形成测定评估血管生成能力。体内通过免疫组织化学和 Western blot 分析检测侵袭和血管生成的标志物，VEGF-A、CD31 和 MMP-9。VEGF-A 被验证为 miR-140-5p 的一个可能的靶基因，并通过双荧光素酶报告基因和 ELISA 得到证实。总之，该研究阐明了 miR-140-5p 抑制乳腺癌转移和血管生成的分子机制，并为开发针对乳腺癌患者的新型 miRNA 靶向抗癌策略提供了有力证据。
