biostudies-literatureWang ZNoncommunicable Chronic Diseases-National Science and Technology Major ProjectScientific Innovation Project of Shanghai Education CommitteeShanghai Shenkang Hospital Development CenterNational Natural Science Foundation of ChinaShanghai Municipal Health Bureau238https://www.ebi.ac.uk/biostudies/studies/S-EPMC12492912biostudies-literatureUnknown24(1)<h4>Background</h4>Resistance to poly (ADP-ribose) polymerase inhibitors (PARPi) poses a major challenge to therapeutic efficacy in castration-resistant prostate cancer (CRPC). Although circular RNAs (circRNAs) have emerged as critical regulators in cancer biology, their involvement in PARPi resistance remains largely uncharacterized.<h4>Objective</h4>This study aims to elucidate the molecular mechanism by which hsa_circ_0038737 modulates PARPi resistance in CRPC through post-transcriptional regulatory pathways.<h4>Methods</h4>We employed a comprehensive set of in vitro and in vivo approaches, including qRT-PCR, RNA sequencing, RNA-protein pull-down, RNA immunoprecipitation, functional assays, and xenograft/organoid models, to investigate the biological function and mechanistic role of hsaMolecular cancerHsa_circ_0038737 promotes PARPi resistance in castration-resistant prostate cancer via IGF2BP3-mediated DNPH1 mRNA stabilization.PMC12492912824745062023ZD05103002021-01-07-00-07-E00080SHDC2025CCS007824033772020CXJQ03Anwaier AZhang ZTian XHong ZQin XYe DFeng TLiu SWang ZXu WGe QfalseHsa_circ_0038737 promotes PARPi resistance in castration-resistant prostate cancer via IGF2BP3-mediated DNPH1 mRNA stabilization.<h4>Background</h4>Resistance to poly (ADP-ribose) polymerase inhibitors (PARPi) poses a major challenge to therapeutic efficacy in castration-resistant prostate cancer (CRPC). Although circular RNAs (circRNAs) have emerged as critical regulators in cancer biology, their involvement in PARPi resistance remains largely uncharacterized.<h4>Objective</h4>This study aims to elucidate the molecular mechanism by which hsa_circ_0038737 modulates PARPi resistance in CRPC through post-transcriptional regulatory pathways.<h4>Methods</h4>We employed a comprehensive set of in vitro and in vivo approaches, including qRT-PCR, RNA sequencing, RNA-protein pull-down, RNA immunoprecipitation, functional assays, and xenograft/organoid models, to investigate the biological function and mechanistic role of hsa2025-01-01T00:00:00Z2025 Oct2026-06-04T02:00:53.222Z2026-05-04T03:13:23.094ZS-EPMC124929124103957510.1186/s12943-025-02447-y