PRMT3-Mediated Arginine Methylation of IGF2BP1 Promotes Oxaliplatin Resistance in Liver Cancer

Authors

Yunxing Shi
Yi Niu
Yichuan Yuan
Kai Li
Chengrui Zhong
Zhiyu Qiu
Keren Li
Zhu Lin
Zhiwen Yang
Dinglan Zuo
Jiliang Qiu
Wei He
Chenwei Wang
Yadi Liao
Guocan Wang
Yunfei Yuan
Binkui Li

Publication Date

4-6-2023

Journal

Nature Communications

Abstract

Although oxaliplatin-based chemotherapy has been effective in the treatment of hepatocellular carcinoma (HCC), primary or acquired resistance to oxaliplatin remains a major challenge in the clinic. Through functional screening using CRISPR/Cas9 activation library, transcriptomic profiling of clinical samples, and functional validation in vitro and in vivo, we identify PRMT3 as a key driver of oxaliplatin resistance. Mechanistically, PRMT3-mediated oxaliplatin-resistance is in part dependent on the methylation of IGF2BP1 at R452, which is critical for the function of IGF2BP1 in stabilizing the mRNA of HEG1, an effector of PRMT3-IGF2BP1 axis. Also, PRMT3 overexpression may serve as a biomarker for oxaliplatin resistance in HCC patients. Collectively, our study defines the PRTM3-IGF2BP1-HEG1 axis as important regulators and therapeutic targets in oxaliplatin-resistance and suggests the potential to use PRMT3 expression level in pretreatment biopsy as a biomarker for oxaliplatin-resistance in HCC patients.

Keywords

Humans, Carcinoma, Hepatocellular, Cell Line, Tumor, Liver Neoplasms, Methylation, Oxaliplatin, Protein-Arginine N-Methyltransferases, Cancer therapy, Tumour biomarkers, Apoptosis

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Associated Data

PMID: 37024475