Molecular mechanisms of transcription factor KLF4-mediated immune infiltration influencing lung adenocarcinoma invasion.

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Lung adenocarcinoma (LUAD) is associated with an increasing incidence and mortality rate while existing treatment strategies continue to exhibit considerable limitation. Studies have demonstrated that upregulation of KLF4 gene inhibits LUAD progression, but its underlying mechanisms remain elusive. The present research explored roles and mechanisms of KLF4 and the NF-κB pathway in LUAD. Lentiviral vectors encoding KLF4 were constructed and transduced into H1299 and A549 cells to generate stable cell lines. These stable cell lines were then injected into BALB/c mice to establish a LUAD model. Subsequently, RNA sequencing, HE staining, immunohistochemistry, ELISA, Western blotting, and flow cytometry were employed to investigate the effects of KLF4 on tumor growth, invasion, immune cell infiltration, and related signaling pathways. Finally, dual-luciferase and in vivo mouse experiments were conducted to validate the molecular mechanisms. KLF4 significantly reduced tumor cell invasion while promoted tumor cell necrosis. Transcriptomic sequencing identified CXCR2 as a target gene and the NF-κB signaling pathway associated with immune infiltration regulation. KLF4 downregulated NF-κB2 and CXCR2 expression, concomitantly decreasing tumor cell invasiveness but increasing levels of CD4+ and CD8+ T cells and macrophages. NF-κB and CXCR2 play an important role in KLF4-mediated immune infiltration, thereby inhibiting tumor invasion and promoting tumor cell apoptosis in mice.