DAZAP2, regulated by miR-125b, contributes to inflammation-related non-small cell lung cancer progression

BACKGROUND: Lung cancer remains the primary cause of cancer-related mortality globally, despite significant advancements in therapeutic strategies. Overall survival rates remain unsatisfactory. Chronic inflammation and microRNAs both play pivotal roles in cancer development. METHODS: This study aimed to elucidate the roles of key microRNAs in inflammation-associated non-small cell lung cancer (NSCLC) development. RESULTS: Our findings reveal a significant reduction in miR-125b expression within NSCLC cell lines when stimulated by IL-10. Furthermore, when stimulated by IFN-γ, the expression levels of miR-125b markedly increase. Enforced expression of miR-125b markedly bolstered cell proliferation, migration, and invasion, while diminishing cell apoptosis. Conversely, inhibition of miR-125b produced opposing effects. Mechanistically, DAZAP2 was identified as a direct regulatory target of miR-125b However, because both miR-125b inhibition and DAZAP2 knockdown suppressed malignant phenotypes, DAZAP2 may represent one component of a broader miR-125b-associated regulatory network rather than the sole mediator of miR-125b function. Combined inhibition of miR-125b and DAZAP2 produced more pronounced tumor-suppressive effects both in vitro and in vivo. CONCLUSIONS: Our data suggest that miR-125b and DAZAP2 are involved in the cytokine-responsive regulatory network of inflammation-related NSCLC progression.