Analysis of gene expression patterns modulated by tuberculous pleural effusion–derived exosomal miRNAs in lung cancer

Introduction Previous pulmonary tuberculosis (TB) is a known risk factor for lung cancer. Earlier studies have demonstrated that tuberculous pleural effusion (TPE)-derived exosomal miRNAs are involved in lung cancer progression. This study aimed to identify potential miRNA–mRNA regulatory pathways contributing to the pathogenesis of TB-associated lung cancer. Methods We isolated Exosomes from the lung effusions of patients with TB and injected intratumorally into lung cancer xenograft mice to model the TB–lung cancer interaction. To identify TB-associated regulators relevant to lung cancer, we first examined differentially expressed miRNAs (DEMs) in exosomes from patients with TB. In parallel, we identified differentially expressed genes (DEGs) in xenograft lung cancer following injection with TB-derived exosomes and analyzed their interactions with the DEMs. Network analysis was then applied to interpret miRNA-mRNA regulatory relationships, with TB-related sub-networks selected for further study. Results In total, five DEMs and 54 DEGs were identified. Pathway enrichment analysis indicated that these DEGs were linked to oxidative phosphorylation, ribosome biogenesis, mitochondrial adenosine triphosphate synthesis, and NADH dehydrogenase activity. Further network analysis with Cytoscape revealed a potential miRNA–mRNA regulatory network encompassing 94 genes expanded from the selected 54 DEGs and 4 DEMs. Finally, in vitro assays validated that the identified cancer-related genes ( NDUFA4 , RPS27 , and COX7A2 ) are involved in regulating miRNA expression. Conclusion In conclusion, our findings suggest potential indirect links between TB-derived exosomal miRNAs and lung cancer associated genes. These results provide a preliminary regulatory framework, and while further functional validation is warranted, they offer exploratory insights into the molecular landscape of TB-associated lung cancer.