Targeting YBX1-m5C mediates RNF115 mRNA circularisation and translation to enhance vulnerability of ferroptosis in hepatocellular carcinoma

Abstract

	•YBX1 inhibits ferroptosis in HCC by regulating the RNF115-DHODH axis.
	•RNF115, an E3 ligase, mediates K27 ubiquitination and autophagic degradation of DHODH.
	•YBX1 binds to the m5C sites of RNF115 mRNA 3′-UTR and interacts with EIF4A1 to bridge the 5′-UTR, promoting mRNA circularisation and translation.
	•High expression of YBX1/RNF115 predicts the poor overall survival in HCC.

Keywords

5-methylcytosine modification / ferroptosis / hepatocellular carcinoma / translational regulation / YBX1

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2025 The Author(s). Clinical and Translational Medicine published by John Wiley & Sons Australia, Ltd on behalf of Shanghai Institute of Clinical Bioinformatics.