The oncogenic role of Ladinin-1 (LAD1), an anchoring filament protein, is largely unknown. In this study, we conducted a series of studies on the oncogenic role of LAD1 in lung adenocarcinoma (LUAD). Firstly, we analyzed the aberrant expression of LAD1 in LUAD and its correlation with patient survival, tumor immune infiltration, and the activation of cancer signaling pathways. Furthermore, the relationship between LAD1 expression and K-Ras and EGF signaling activation, tumor cell proliferation, migration, and colony formation was studied by gene knockout/knockout methods. We found that LAD1 was frequently overexpressed in LUAD, and high LAD1 expression predicts a poor prognosis. LAD1 exhibits promoter hypomethylation in LUAD, which may contribute to its mRNA upregulation. Single-sample gene set enrichment analysis (ssGSEA) showed that acquired immunity was negatively correlated with LAD1 expression, which was verified by the downregulated GO terms of “Immunoglobulin receptor binding” and “Immunoglobulin complex circulating” in the LAD1 high-expression group through Gene Set Variation Analysis (GSVA). Notably, the Ras-dependent signature was the most activated signaling in the LAD1 high-expression group, and the phosphorylation of downstream effectors, such as ERK and c-jun, was strongly inhibited by LAD1 deficiency. Moreover, we demonstrated that LAD1 depletion significantly inhibited the proliferation, migration, and cell-cycle progression of LUAD cells and promoted sensitivity to Gefitinib, K-Ras inhibitor, and paclitaxel treatments. We also confirmed that LAD1 deficiency remarkably retarded tumor growth in the xenograft model. Conclusively, LAD1 is a critical prognostic biomarker for LUAD and has potential as an intervention target.

NF-κB, a multifunctional transcription factor, is linked to cancer initiation and progression. As a key immune mediator, it may play a crucial role in HPV-induced cervical carcinogenesis. However, consensus is lacking on the activation timing of NF-κB during the transition from cervical intraepithelial neoplasia (CIN) to cervical squamous cell carcinoma (CSCC). In this study, immunohistochemical analysis was performed to examine RELA, one of the important members of the NF-κB family, and phospho-RELA expression in different cervical lesions. Then, we analyzed NF-κB regulation of differentially expressed genes (DEGs) in cervical lesions vs. normal tissues. Gene enrichment identified oncogenic DEGs, followed by expression and survival analyses. The impact of NF-κB activation on cervical cell proliferation, migration, and oncogenic regulation, as well as the effects of inhibiting NF-κB, were examined. Our study showed that NF-κB activation starts in cervical simple hyperplasia and intensifies as CIN evolves to CSCC. NF-κB-regulated DEGs show stage-specific functions: immune regulation in CIN and cancer promotion in CSCC. Short-term NF-κB activation boosts cervical cell proliferation and migration, which is reversible by an NF-κB inhibitor. Long-term NF-κB activation promotes the expression of cancer-promoting genes in normal cells and also maintains them in cancer tissues, which is linked to poorer prognosis. Inhibiting NF-κB downregulates these genes in cancer cells and suppresses the oncogenic abilities of cervical cancer cells. Collectively, NF-κB activation initiates during the simple hyperplasia stage of cervical cells, stimulating proliferation, migration, and oncogene expression. Throughout the transition from CIN to CSCC, NF-κB activation progressively intensifies, and its long-term activation promotes carcinogenesis. Thus, NF-κB is crucial in mediating cervical oncogenic transformation.