PDF(Pubmed)
Abstract：
As carriers containing abundant biological information, exosomes could deliver the property of donor cells to recipient cells. Emerging studies have shown that tumor cells could secrete a mass of exosomes into the microenvironment to regulate bystander cells. However, the underlying mechanisms of such a phenomenon remain largely unexplored. In this research, we purified and identified the exosomes of A549 cells and found that A549-cell-derived exosomes promoted BEAS-2B cells migration, invasion, and epithelial-mesenchymal transition (EMT). Importantly, we observed that let-7c-5p and miR-181b-5p were attenuated in A549-cell-derived exosomes compared to BEAS-2B-cell-derived exosomes. The analysis of miRNA expression level in BEAS-2B cells indicated that incubation with A549-cell-derived exosomes reduced the expression levels of let-7c-5p and miR-181b-5p. In transient transfections assay, we found that downregulation of let-7c-5p and miR-181b-5p simultaneously showed stronger promotion of BEAS-2B cells migration and invasion than individually. Moreover, exosomes secreted from A549 cells with upregulated expression of let-7c-5p and miR-181b-5p significantly reduce their regulatory effect on BEAS-2B cells. Bioinformatics analyses revealed that let-7c-5p and miR-181b-5p inhibit the EMT process mainly by regulating focal adhesion and mitogen-activated protein kinase (MAPK) signaling pathway. Thus, our data demonstrated that A549-cell-derived exosomal let-7c-5p and miR-181b-5p could induce migration, invasion, and EMT in BEAS-2B cells, which might be regulated through focal adhesion and MAPK signaling pathway. The expression level of let-7c-5p and miR-181b-5p may show great significance for the early diagnosis of lung cancer.
摘要：
作为含有丰富生物信息的载体,外泌体可以将供体细胞的特性传递给受体细胞。新兴的研究表明，肿瘤细胞可以分泌大量的外泌体进入微环境，以调节旁观者细胞。然而,这种现象的潜在机制在很大程度上仍未被探索。在这项研究中,我们纯化并鉴定了A549细胞的外泌体，发现A549细胞来源的外泌体促进BEAS-2B细胞的迁移，入侵,和上皮-间质转化（EMT）。重要的是,我们观察到,与BEAS-2B细胞来源的外泌体相比,let-7c-5p和miR-181b-5p在A549细胞来源的外泌体中减弱.BEAS-2B细胞中miRNA表达水平的分析表明，与A549细胞衍生的外泌体一起孵育降低了let-7c-5p和miR-181b-5p的表达水平。在瞬时转染试验中,我们发现,let-7c-5p和miR-181b-5p的下调同时显示出比单独更强的BEAS-2B细胞迁移和侵袭的促进作用.此外，从A549细胞分泌的外泌体表达上调let-7c-5p和miR-181b-5p显著降低其对BEAS-2B细胞的调节作用。生物信息学分析显示，let-7c-5p和miR-181b-5p主要通过调节粘着斑和丝裂原活化蛋白激酶（MAPK）信号通路抑制EMT过程。因此，我们的数据表明，A549细胞来源的外泌体let-7c-5p和miR-181b-5p可以诱导迁移，入侵,和BEAS-2B细胞中的EMT，可能通过粘着斑和MAPK信号通路进行调节。let-7c-5p和miR-181b-5p的表达水平对肺癌的早期诊断具有重要意义。
