{"database":"ENA","file_versions":[],"scores":null,"additional":{"omics_type":["Genomics"],"center_name":["李宗伟Lab, 细胞生物学, 安徽医科大学"],"full_dataset_link":["https://www.ebi.ac.uk/ena/browser/view/PRJNA1227882"],"scientific_name":["Homo sapiens"],"long_description":["Albeit being recognized as one of the major mesenchymal cells and a dangerous accomplice in myeloma, the roles of adipocytes in different stages of myeloma pathogenesis remain elusive. Here we showed that glucose metabolic stress impairs protein stability of interferon regulatory factor 4 (IRF4), an oncoprotein essential for myeloma cell survival, while adipocytes-derived β-hydroxybutyrate (β-OHB) preserves IRF4 stability and cell survival. Mechanistically, glucose deficiency activates the AMP-activated protein kinase (AMPK) to disrupt the interaction of IRF4 with heat shock protein 90 (HSP90), enabling the E3 ligase TRIM21-mediated IRF4 ubiquitination degradation. The presence of β-OHB drives 3-oxoacid CoA-transferase 1 (OXCT1)-mediated ketolysis and facilitates N-acetyltransferase 10 (NAT10)-mediated IRF4 acetylation at lysine 87, which restores IRF4’s interaction with HSP90 and precludes TRIM21-mediated IRF4 degradation. Notably, targeting OXCT1 or NAT10 to interfere with β-OHB utilization displays a synergistic anti-myeloma effect in combination with AMPK activator both in vitro and in vivo. Our study thus positions adipocytes-derived β-OHB as a pivotal contributor that enables myeloma cells to overcome glucose metabolic stress and suggests viable therapeutic targets to be exploited for multiple myeloma treatment. Overall design: Addition of glucose, glucose deficiency, β - OHB, and combined treatment to ARP1 cells，Collect cells for cuttaq detection after processing"],"repository":["ENA"],"additional_accession":[]},"is_claimable":false,"name":"Adipocytes-derived β-hydroxybutyrate confers the resistance of myeloma cells to metabolic stress","description":"Adipocytes-derived β-hydroxybutyrate confers the resistance of myeloma cells to metabolic stress","dates":{"last_updated":"2025-09-24","first_public":"2025-06-29"},"accession":"PRJNA1227882","cross_references":{"GEO":["GSE290392"],"taxon":["9606"]}}