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

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.

This study aimed to elucidate the roles of key microRNAs in inflammation-associated non-small cell lung cancer (NSCLC) development.

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.

Our data suggest that miR-125b and DAZAP2 are involved in the cytokine-responsive regulatory network of inflammation-related NSCLC progression.