This study tried to explore the molecular mechanism underlying progression of lung adenocarcinoma (LUAD) and discuss the extracellular communication between cancer cells and vascular endothelial cells. Roughly, differential analysis was carried out to note that miR-30a-5p was lowly expressed in LUAD, whereas CCNE2 was highly expressed. Cell functional experiments demonstrated that overexpressed miR-30a-5p led to suppressed cell abilities in proliferation, migration and invasion. Dual-luciferase reporter gene assay and RNA immunoprecipitation verified the binding of miR-30a-5p and CCNE2, as well as decreased mRNA and protein expression of CCNE2 with miR-30a-5p overexpression. Simultaneous up-regulation of miR-30a-5p and CCNE2 reversed the promotion of CCNE2 on malignant behaviors of LUAD cells. In vivo mice experiments exhibited that high miR-30a-5p expression hindered tumor growth. Additionally, miR-30a-5p was localized on the Extracellular Vesicles microRNA (EVmiRNA) database. MiR-30a-5p was abundant in exosomes derived from vascular endothelial cells. To validate that miR-30a-5p could be delivered to LUAD cells via exosomes and then make an effect, exosomes from vascular endothelial cells were first extracted and identified by transmission electron microscopy and detection of exosomal marker proteins (Alix, CD63, TSG101). Sequentially, the extracted exosomes were labeled with DIO to note that exosomes could be internalized by cancer cells. Further experiments indicated that miR-30a-5p was increased in cancer cells co-cultured with exosomes, which in turn suppressed cell malignant behaviors and made cell cycle arrest. In all, our findings clarified that exosomes derived from vascular endothelial cells delivered miR-30a-5p to LUAD cells to affect tumor malignant progression via the miR-30a-5p/CCNE2 axis.

中文翻译：

---

血管内皮细胞衍生的外泌体 miR-30a-5p 通过靶向 CCNE2 抑制肺腺癌恶性进展。

本研究试图探索肺腺癌（LUAD）进展的分子机制，并讨论癌细胞与血管内皮细胞之间的细胞外通讯。粗略地，进行差异分析以注意到 miR-30a-5p 在 LUAD 中低表达，而 CCNE2 高表达。细胞功能实验表明，过表达的 miR-30a-5p 导致细胞增殖、迁移和侵袭能力受到抑制。双荧光素酶报告基因检测和 RNA 免疫沉淀证实了 miR-30a-5p 和 CCNE2 的结合，以及随着 miR-30a-5p 过表达，CCNE2 的 mRNA 和蛋白质表达降低。miR-30a-5p 和 CCNE2 的同时上调逆转了 CCNE2 对 LUAD 细胞恶性行为的促进作用。体内小鼠实验表明，高 miR-30a-5p 表达阻碍了肿瘤生长。此外，miR-30a-5p 位于细胞外囊泡 microRNA (EVmiRNA) 数据库中。MiR-30a-5p 在源自血管内皮细胞的外泌体中含量丰富。为了验证 miR-30a-5p 可以通过外泌体传递给 LUAD 细胞并产生作用，首先从血管内皮细胞中提取和鉴定外泌体，通过透射电子显微镜和外泌体标记蛋白（Alix、CD63、TSG101）的检测进行鉴定。随后，提取的外泌体用 DIO 标记，以表明外泌体可以被癌细胞内化。进一步的实验表明，与外泌体共培养的癌细胞中 miR-30a-5p 增加，进而抑制细胞恶性行为并使细胞周期停滞。在所有，