ENA0000GenomicsLoring, Regenerative Medicine, The Scripps Research Institutehttps://www.ebi.ac.uk/ena/browser/view/PRJNA120215Mus musculusNeuroendocrine (NE) carcinoma and NE differentiation (NED) of human prostate tumor are hallmarks of aggressive human prostate cancer. Here we reveal that HIF-1a cooperation with FoxA2, a transcription factor expressed in NE tissue, is required for determining NE phenotype. Reduced HIF-1a expression, as seen in the E3 ubiquitin ligase Siah2 mutant mice, converted NE tumors to atypical hyperplasia when crossed with the TRAMPTg mice. Significantly, HIF-1a cooperation with FoxA2 enables the trans-activation of select HRE-regulated genes such as Hes6, Plod2 and Jmjd1a, whose expression is notably higher in metastatic prostate adenocarcinomas. Our findings disclose the requirement for spatial and timely regulation of FoxA2 and HIF-1a for NE/NED in prostate tumors. Overall design: 12 prostate tumor samples were analyzed during normoxia and hypoxia, with different FOX/HIF genotypes. The pivotal samples are represented as duplicates.ENASinh2, single-organism biosynthetic process, Prostates, Tcf3b, Activity, HNF3beta, formation, anabolism, cell process disease, tumor disease, neoplasia, xsiah2, neoplastic disease, biosynthesis, TCF3B, disease of cellular proliferation, Tcf-3b, neoplasm (disease)., synthesis, Hnf3b, neoplastic growth, Hnf-3b, siah2-A, Xsiah-2, male prostate, AA415433, HNF3B, HNF3-beta, tumor, hSiah2, other neoplasm, prostate, neoplasm, General activity, multicellular organismal biosynthetic process, prostatamouse, mouse <Mus musculus>, house mouse.0.00.00.00.00.00falseMus musculusSiah2-dependent concerted activity of HIF and FoxA2 regulates formation of neuroendocrine prostate tumors2022-05-122014-02-11PRJNA120215GSE184782060935010090