Vascular endothelial cell-derived exosomal miR-30a-5p inhibits lung adenocarcinoma malignant progression by targeting CCNE2.

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.