{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Jin X"],"funding":["Natural Science Foundation of Guangdong Province (Guangdong Natural Science Foundation)","National Natural Science Foundation of China (National Science Foundation of China)"],"pagination":["466-479"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC11894169"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["32(3)"],"pubmed_abstract":["Oxaliplatin-based therapeutics is a widely used treatment approach for hepatocellular carcinoma (HCC) patients; however, drug resistance poses a significant clinical challenge. Epigenetic modifications have been implicated in the development of drug resistance. In our study, employing siRNA library screening, we identified that silencing the m<sup>6</sup>A writer METTL3 significantly enhanced the sensitivity to oxaliplatin in both in vivo and in vitro HCC models. Further investigations through combined RNA-seq and non-targeted metabolomics analysis revealed that silencing METTL3 impeded the pentose phosphate pathway (PPP), leading to a reduction in NADPH and nucleotide precursors. This disruption induced DNA damage, decreased DNA synthesis, and ultimately resulted in cell cycle arrest. Mec"],"journal":["Cell death and differentiation"],"pubmed_title":["METTL3 confers oxaliplatin resistance through the activation of G6PD-enhanced pentose phosphate pathway in hepatocellular carcinoma."],"pmcid":["PMC11894169"],"funding_grant_id":["2021A1515010707","82202905","82172646","82173016","81972227"],"pubmed_authors":["Duan J","Jin X","Chen J","Cai M","Lv Y","Wang F","Bi J","Lu L","Xie D","Dai M","Ma C","Li S","Bie F","Xu S","Zhou J"],"additional_accession":[]},"is_claimable":false,"name":"METTL3 confers oxaliplatin resistance through the activation of G6PD-enhanced pentose phosphate pathway in hepatocellular carcinoma.","description":"Oxaliplatin-based therapeutics is a widely used treatment approach for hepatocellular carcinoma (HCC) patients; however, drug resistance poses a significant clinical challenge. Epigenetic modifications have been implicated in the development of drug resistance. In our study, employing siRNA library screening, we identified that silencing the m<sup>6</sup>A writer METTL3 significantly enhanced the sensitivity to oxaliplatin in both in vivo and in vitro HCC models. Further investigations through combined RNA-seq and non-targeted metabolomics analysis revealed that silencing METTL3 impeded the pentose phosphate pathway (PPP), leading to a reduction in NADPH and nucleotide precursors. This disruption induced DNA damage, decreased DNA synthesis, and ultimately resulted in cell cycle arrest. Mec","dates":{"release":"2025-01-01T00:00:00Z","publication":"2025 Mar","modification":"2025-04-22T20:51:26.135Z","creation":"2025-04-06T03:20:24.69Z"},"accession":"S-EPMC11894169","cross_references":{"pubmed":["39472692"],"doi":["10.1038/s41418-024-01406-2"]}}