NFYB (nuclear transcription factor Y subunit beta) is a component of the heterotrimeric NF-Y transcription factor complex that recognizes CCAAT-box motifs in gene promoters 1. It functions as a sequence-specific DNA-binding transcription regulator that can act as both an activator and repressor depending on cofactor interactions 1. Mechanistically, NFYB regulates transcription through several pathways. In glioblastoma, NFYB activates HDAC5 to inhibit SHMT2 expression, reducing glycolysis and chemoresistance 1. In colorectal cancer, NFYB transactivates E2F1, which subsequently induces CHK1 expression to promote oxaliplatin resistance 2. NFYB also collaborates with other transcription factors like B-Myb to regulate cell cycle genes and enhancers 3. Additionally, NFYB activates PROS1 transcription in fibroblasts to promote papillary thyroid microcarcinoma progression through MERTK/WNT/TGF-β signaling 4. Clinically, elevated NFYB expression is associated with worse outcomes across multiple cancers. High NFYB predicts poor survival in gastric cancer patients, correlating with advanced T stage and cancer-associated fibroblast infiltration 5. In glioblastoma, NFYB knockdown inhibits proliferation, invasion, and migration, with expression linked to oxidative phosphorylation pathway activity and recurrence 6. NFYB also shows potential diagnostic value in recurrent pregnancy loss assessment 7.