Exosome-derived Uc.339 as a potential biomarker for bone metastasis from pulmonary adenocarcinoma.

Abstract

This study explored the role of Uc.339, which is a highly expressed genomic sequence in tumor cell-derived exosomes, in mediating bone metastasis from lung adenocarcinoma. By integrating clinical samples, in vitro experiments, and in vivo murine models, we elucidated the molecular mechanisms underlying this process. Clinical blood samples from patients with lung adenocarcinoma revealed elevated Uc.339 expression in exosomes, particularly in those with bone metastasis. In vitro experiments using A549 cell-derived exosomes demonstrated an increase in osteoclast formation, implicating Uc.339 in bone microenvironment modulation. Mechanistically, Uc.339 functions as a decoy for miR-339-3p, disrupting the gene expression balance. In vivo experiments in a murine model confirmed disrupted bone microstructure in the presence of elevated Uc.339, alongside altered expression of key regulators, including SQSTM1, RANKL, nuclear factor kappa B, and miR-339-3p. Our findings underscore the systemic impact of Uc.339 in exosomes, suggesting its potential as both a biomarker and a mediator of bone metastasis. Moreover, the identified molecular alterations provide potential therapeutic targets for managing bone metastasis in patients with lung adenocarcinoma. This study contributes to a deeper understanding of the complex interplay between cancer cells and the bone microenvironment, paving the way for targeted interventions and improved clinical outcomes.