PCBP2 Mediates Olaparib Resistance in Breast Cancer by Inhibiting m6A Methylation to Stabilize PARP1 mRNA.

ABSTRACT: Base excision repair (BER), a critical pathway for repairing DNA single-strand breaks, is mediated by PARP, which plays a pivotal role in maintaining genomic stability. Targeting PARP with PARP inhibitors (PARPi) has emerged as an effective strategy for treating BRCA-mutated breast cancers characterized by homologous recombination deficiency. However, PARPi resistance remains a major challenge in the treatment of BRCA-mutated breast cancer. Using bioinformatics analysis and cellular-level experiments, we discovered that the RNA-binding protein PCBP2 contributes to resistance to the PARPi olaparib in BRCA-mutated breast cancer by increasing PARP1 expression via interference with the m6A methylation machinery. PCBP2 was upregulated in olaparib-resistant cells, and PCBP2 overexpression in BRC

SUBMITTER: Qi Z 

PROVIDER: S-EPMC12521917 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature