BE screen reveals METTL3 S2 dephosphorylation sensitizes gastric cancer cells to oxaliplatin by interfering METTL3-eIF3H interaction.

ABSTRACT: The resistance to oxaliplatin (OXA)-based chemotherapies may lead to poor prognosis in patients with gastric cancer (GC). Emerging evidence suggests that resistance is closely associated with phosphorylation modifications. In GC cell line AGS, high-throughput base editor screen identified key phosphorylation sites associated with OXA response. Methyltransferase-like 3 (METTL3) S2 emerged as a notable negative hit. Further investigation revealed that dephosphorylation of METTL3 S2 disrupted the METTL3-eukaryotic translation initiation factor 3 subunit H (eIF3H) interaction, thereby suppressing the translation of oncogenes involved in replication stress responses, including bromine domain protein 4 (BRD4) and serpin family E member 2 (SERPINE2), ultimately enhancing sensitivity

SUBMITTER: Xu X 

PROVIDER: S-EPMC12700196 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature