Exosomal miR-499a-5p promotes cell proliferation, migration and EMT via mTOR signaling pathway in lung adenocarcinoma
Exosomal miR-499a-5p promotes cell proliferation, migration and EMT via mTOR signaling pathway in lung adenocarcinoma
复制标题
外泌体miR-499a-5p通过mTOR信号通路促进肺腺癌细胞增殖、迁移和EMT
DOI：
10.1016/j.yexcr.2019.03.035
复制
发表时间：
2019-06-15
影响因子：
3.7
通讯作者：
Lu, Shun
中科院分区：
文献类型：
--
作者：
He, Shan;Li, Ziming;Lu, Shun
肿瘤源性外泌体含有信息丰富的microrna，参与癌变、细胞迁移、侵袭和上皮-间质转化（EMT），最终促进癌症转移。本研究旨在阐明外泌体miRNA影响肿瘤癌变和转移的机制和机制。其中，miR-499a-5p在高转移肺癌细胞系及其外泌体中均上调。MiR-499a-5p过表达促进细胞增殖、迁移和EMT，而MiR-499a-5p敲低在体外抑制这些过程。拮抗剂抑制miR-499a-5p在体内抑制肿瘤生长。因此，来自高转移细胞系的富含mir499a的外泌体通过mTOR途径增强了细胞增殖、迁移和EMT，而miR-499a-5p抑制剂可以抑制这种作用。该研究揭示了癌源性外泌体miR-499a-5p的潜在诊断和治疗价值，并揭示了一种新的调节转移的分子机制。
Tumor-derived exosomes contain informative microRNAs involved in carcinogenesis, cell migration, invasion and epithelial-mesenchymal transition (EMT), eventually contributing to metastasis of cancers. This study aims to clarify which and how exosomal miRNA affects tumor carcinogenesis and metastasis. Among them, miR-499a-5p was upregulated in both highly metastatic lung cancer cell line and their exosomes. MiR-499a-5p over-expression promoted cell proliferation, migration and EMT, while miR-499a-5p knockdown suppressed these processes in vitro. Inhibition of miR-499a-5p by antagomirs administration restrained tumor growth in vivo. Consequently, miR499a-sufficient exosomes, derived from highly metastatic cell line, enhanced cell proliferation, migration and EMT via mTOR pathway, and the effect could be inhibited by miR-499a-5p inhibitor. The study reveals the potential diagnostic and therapeutic value of cancer-derived exosomal miR-499a-5p, and sheds a new insight on a novel molecular mechanism which modulates metastasis.