Faculty, Staff and Student Publications
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
DOI
10.1038/s41467-023-37542-5
PMID
37024475
PMCID
PMC10079833
PubMedCentral® Posted Date
April 2023
PubMedCentral® Full Text Version
Post-print
Published Open-Access
yes
Included in
Bioinformatics Commons, Biomedical Informatics Commons, Medical Sciences Commons, Oncology Commons
Comments
Associated Data
PMID: 37024475