Tumor-derived exosomal miR-199b-5p promotes proliferation and epithelial-mesenchymal transition in non-small cell lung cancer by targeting CCNL1

作者：Bangzhu Liu, Rui Yan, Miao Li, Linian Huang · 发表于：Translational Oncology · 年份：2025 · DOI：10.1016/j.tranon.2025.102564 · 研究领域：Extracellular vesicles in disease、MicroRNA in disease regulation、Circular RNAs in diseases

OBJECTIVE: To explore the effect of exosome-mediated miR-199b-5p on lung cancer cells behavior, intrapulmonary metastasis, and its underlying mechanism. METHODS: Exosomes from SK-LU-1 cells overexpressing has-miR-199b-5p (miR-199b-5p) were used to treat A549 or H299 cells. Cell motility was evaluated using wound scratch healing and transwell assays. Gene and protein expression were detected by quantitative real-time PCR (QRT-PCR) and Western blot. Target genes of miR-199b-5p were predicted through multiple-database analysis and validated. RESULTS: Transmission electron microscopy (TEM) demonstrated isolated exosomes had a typical bilayer membrane (30-100 nm). miR-199b-5p was highly expressed in lung cancer cells and detectable in the serum of lung cancer patients, with the highest levels observed in SK-LU-1 cells and their derived exosomes. Exosomal miR-199b-5p significantly enhanced the motility of A549 and H1299 cells and upregulated the expression of epithelial-mesenchymal transition (EMT)-related proteins. Exosomes promoted lung metastasis of H1299 cells and inhibited the expression of Cyclin L1 (CCNL1). Either CCNL1 inhibition or miR-199b-5p overexpression significantly promoted H1299 cell proliferation and reduced apoptosis, while CCNL1 overexpression inhibited cell motility. Protein-protein interaction (PPI) network, Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses indicated involvement of the Wnt/β-catenin signaling pathway in th...