| Background and Objective As the most common form of renal cell carcinoma(RCC),clear cell renal cell carcinoma(cc RCC)is a serious threat to patients’ health.Activation of NF-κB signaling contributes to tumorigenesis and progression.However,the mechanism of NF-κB signaling activation and its relationship with lipid metabolism remain unclear.MethodsAberrant NF-κB signaling and metabolic alterations were highlighted by sequencing of three pairs of cc RCC and adjacent normal tissues.KAT2 B was identified as a novel NF-κBand metabolism-related biomarker in cc RCC by bioinformatics analysis and validated by q RT-PCR,western blots,and IHC.The promoter methylation of KAT2 B was determined by methylation-specific polymerase chain reaction(PCR)(MSP).The regulatory mechanism of KAT2 B was investigated by immunoprecipitation,mass spectrometry analysis,immunofluorescence staining,immunoblot analysis,and cycloheximide treatment.The lipid metabolism was determined by LC-MS/MS,oil red O staining,Nile red staining,and triglyceride kit.A series of functional analyses were conducted in cell lines and xenograft models.Finally,functional analyses were performed in vitro and in vivo using the CCK-8assay,transwell assay,subcutaneous graft tumor animal model,and tail vein transfer animal model.Results1.KAT2 B is lowly expressed in cc RCC.2.Hypermethylation of the KAT2 B promoter leads to low KAT2 B expression in cc RCC.3.KAT2 B inhibits the proliferation,migration,and invasion of cc RCC.4.KAT2 B inhibits lipid accumulation in cc RCC through inhibition of NF-κB signaling.5.KAT2 B inhibits NF-κB signalling by acetylating HDAC5 and reducing the stability of LSD1.ConclusionsCollectively,these findings clarify the tumor suppressor role of KAT2 B and reveal a potential regulatory relationship between the NF-κB signaling and lipid metabolism in cc RCC,which could provide a new target and direction for the medical treatment of cc RCC in the future. |
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