Center for Cell Therapy, The Affiliated Hospital of Jiangsu University, Zhenjiang, 212001, Jiangsu, PR China; School of Pharmacy, Nantong University, Nantong, 226001, Jiangsu, PR China.
School of Laboratory Medicine, Ningxia Medical University, Yinchuan, 750004, PR China.
Int J Biochem Cell Biol. 2018 Apr;97:43-51. doi: 10.1016/j.biocel.2018.02.005. Epub 2018 Feb 6.
Metastastic breast cancer, especially triple-negative (TN), is one of the most common causes of cancer related deaths in women. Recent years, tumor-associate vessel formation is considered as a more generally and effective target to patient with malignant cancer. Our previous studies indicated that miR-19b-1 controls the intrinsic angiogenic activity of human umbilical vein endothelial cells (HUVECs) in vitro. In this study, in silico analysis indicated VEZF1 that implicates in angiogenesis and triple-negative breast cancer progression might be the target of miR-19b-1. Further investigation showed that overexpressing miR-19b-1 in human triple-negative breast cancer cell line(MDA-MB-231) led to impaired angiogenic activity of HUVECs in vitro and in vivo. Additionally, miR-19b-1 upregulation inhibited the vessel imitation mediated by MDA-MB-231. Furthermore, enforced expression of miR-19b-1 in MDA-MB-231 has impact on HUVECs apoptosis and altered the mitochondrial membrane potential, which suggested the possible mechanism involved in interaction between breast cancer and endothelial cells. What's more, we found that miR-19b-1 stable overexpression in MDA-MB-231 caused tumor growth arresting entirely. Besides, our results suggested that miR-19b-1 could inhibit angiogenesis by possibly targeting VEGF receptor endocytosis signaling pathway. Taking together, our findings suggest an important role of miR-19b-1 in crosstalk between metastatic breast cancer and endothelial cells and provide us new insights for exploring miR-19b-1 and its multiple targets as promising therapeutic candidates to interfere breast cancer progression.
转移性乳腺癌，特别是三阴性（TN），是女性癌症相关死亡的最常见原因之一。近年来，肿瘤相关血管形成被认为是恶性癌症患者更普遍和有效的治疗靶点。我们之前的研究表明，miR-19b-1 可以控制人脐静脉内皮细胞（HUVEC）的内在血管生成活性。在这项研究中，计算机分析表明，VEZF1 可能是 miR-19b-1 的靶点，它参与血管生成和三阴性乳腺癌的进展。进一步的研究表明，在人三阴性乳腺癌细胞系（MDA-MB-231）中过表达 miR-19b-1 导致体外和体内 HUVEC 的血管生成活性受损。此外，miR-19b-1 的上调抑制了 MDA-MB-231 介导的血管模仿。此外，miR-19b-1 在 MDA-MB-231 中的强制表达对 HUVEC 凋亡有影响，并改变了线粒体膜电位，这表明乳腺癌和内皮细胞之间相互作用可能涉及的机制。更重要的是，我们发现 miR-19b-1 在 MDA-MB-231 中的稳定过表达完全阻止了肿瘤生长。此外，我们的结果表明，miR-19b-1 可能通过靶向 VEGF 受体内吞信号通路抑制血管生成。总之，我们的研究结果表明，miR-19b-1 在转移性乳腺癌和内皮细胞之间的相互作用中起着重要作用，并为我们提供了新的见解，以探索 miR-19b-1 及其多个靶点作为有前途的治疗候选物，以干扰乳腺癌的进展。
