NFKB2 (Nuclear Factor Kappa B Subunit 2)

P2, N=20, Active, not recruiting, Pharming Technologies B.V. | Recruiting --> Active, not recruiting

Our study identified PLK1 as a key regulator of β-catenin signaling flexibility in CRC, coordinating kinase-dependent and transcriptional mechanisms to sustain pathway activation. The discovery of the PLK1-NFKB2-USP2a-β-catenin axis provides a novel therapeutic rationale for targeting PLK1 to selectively disrupt Wnt-driven tumorigenesis, potentially overcoming the toxicity limitations of conventional Wnt inhibitors.

Additionally, a microbial prognostic-predictive signature was established comprising Succinimonas, Collimonas, and Marichromatium, which also exhibited potential for indicating immunotherapeutic benefit and predicting drug sensitivity to cisplatin, cytarabine, pyrimethamine, olaparib, bicalutamide and vorinostat in LUAD treatment. This study identified intratumoral microbes associated with metabolism, revealed distinct subtypes and their roles in LUAD, and established a predictive signature for the prognosis and therapeutic responsiveness of LUAD.

Additionally, we identified four potential drug targets, including PFAS, EIF2S3, EIF6, and NFKB2. Molecular docking analysis suggested that neratinib, a clinically approved drug, could serve as a promising therapeutic agent for GSRCC, offering new avenues for clinical intervention.

By engaging with naive T cells through HLA-DRA via ligand-receptor interactions, CD74⁺ B cells activate transcription factors, including NFKB1, NFKB2, NFATC1, NFATC2, FOS, and RUNX1, in naive T cells, thereby enhancing the immune response. Consequently, CD74⁺ B cells represent a compelling biomarker for and therapeutic target of PSCC, offering profound insights into the immunological mechanisms that drive PSCC progression and response to immunotherapy.

In vivo experiments showed that NFKB2 knockdown inhibited tumor growth and the expansion of CD8+PDCD1+ T cells, effects that were reversible with corticosterone treatment (all P < 0.05). Collectively, a glucocorticoid signaling-related gene signature was developed and rigorously validated as a predictive tool for prognosis and immunotherapeutic response in KIRC, offering valuable insights for guiding personalized treatment strategies.

Our single-cell analysis details the EC TME landscape, revealing robust communication between M2_like2 macrophages and SOX9+LGR5- epithelial cells. We highlight a key mechanism where NFKB2 mediates MIF's pro-tumorigenic effects via the CD44 receptor, offering new insights into EC progression and potential therapeutic targets.

This study identified key genes involved in cytokine dysregulation in cytarabine-resistant HL60 cells, providing potential targets for overcoming drug resistance in AML. These findings offer new avenues for the development of more effective therapies for relapsed or refractory AML patients.

Our results highlight the importance of a combinational strategy employing both epigenetic and immunotherapy in HNSCC.

Several senescence regulators (CDKN1A, CDKN2B, and E2F3), ECM remodeling genes (MMP10 and TIMP2), and NF-κB-driven SASP factors (CCL2, CXCL2, NFKB1, and NFKB2) were significantly downregulated in adenocarcinomas, indicating the resolution of senescence-associated inflammatory signaling during tumor progression. These findings support the predominance of OIS phenotypes in colorectal adenomas, suggesting their potential role as a temporary barrier to tumorigenesis in colorectal cancer.

We revealed a positive correlation between the Nscore and macrophage M1, suggesting potential drug response mechanisms. Based on the identified AML subtypes and their distinct mutational landscapes, we predicted potential treatment options, with Paclitaxel, Afuresertib, and Mitoxantrone emerging as potential therapeutic agents for the AML subtypes.

Key genes (Nfkb1, Nfkb2, Malt, Lta, Ltb, Tnf) and proteins (P50, P100) in the NF-κB pathway are upregulated, indicating the crucial role of the NF-κB pathway in M2 macrophage polarization. This study offers crucial evidence regarding the role of the NF-κB signaling pathway in modulating F. nucleatum-induced macrophage M2 polarization, underscoring its significance in the progression of colorectal cancer.