Exosome-derived microRNA-433 inhibits tumorigenesis through incremental infiltration of CD4 and CD8 cells in non-small cell lung cancer

摘要

Tumor-derived exosomal microRNAs (miRNAs/ miRs) serve a vital biological role in tumorigenesis and development, but the effects and underlying mechanisms remain unclear. To explore the impact of exosomal miR-433 in non-small cell lung cancer (NSCLC) and understand its mechanism of action in NSCLC progression, the present study isolated the exosomes from the plasma of patients with NSCLC after chemotherapy and found that miR-433 expression was lower in plasma of patients with resistant NSCLC compared with in plasma of patients with sensitive NSCLC and in normal serum. Additionally, miR-433 expression was markedly negatively associated with a large tumor size, distant metastasis, advanced TNM stage and a poor prognosis in patients with NSCLC. miR-433 inhibited tumor growth by blocking the cell cycle in vitro and in vivo, as well as by promoting apoptosis and T-cell infiltration in the tumor microenvironment. Additionally, miR-433 inhibited chemo-resistance to cisplatin by regulating DNA damage. Moreover, miR-433 inactivated the WNT/beta-catenin signaling pathway by targeting transmembrane p24 trafficking protein 5 in NSCLC. Overall, the current findings may provide a potential prognostic biomarker and therapeutic target for patients with NSCLC.