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The E3 ubiquitin ligase RNF112 inhibits bladder cancer progression by attenuating lipid synthesis through the degradation of c-Myc

ABSTRACT: The E3 ubiquitin ligase RNF112 exhibits significant downregulation in bladder cancer, correlating with disease progression and unfavorable prognosis. Experimental evidence from in vitro and in vivo studies indicates that RNF112 suppresses bladder cancer proliferation, migration, and lipid synthesis. Mechanistically, RNF112 interacts directly with the MBII domain of MYC through its N-terminal zinc finger motif. The catalytic site C97 of RNF112 facilitates K48-linked polyubiquitination of the K389 residue on the c-Myc protein, accelerating its degradation. The restoration of c-Myc expression has been shown to mitigate the inhibitory impacts of RNF112 on the growth, migration, and lipid synthesis of bladder cancer cells. Additionally, our research validates the interaction of c-Myc with the ACLY promoter, leading to an enhancement of its transcriptional activity. RNF112 exerts its inhibitory effects on lipid synthesis in bladder cancer through the regulation of c-Myc. In conclusion, RNF112 suppresses the proliferation, migration, and lipid synthesis of bladder cancer cells by facilitating the ubiquitin-mediated degradation of c-Myc.

ORGANISM(S): Homo sapiens

PROVIDER: GSE270143 | GEO | 2025/04/01

REPOSITORIES: GEO

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