Targeting NAT10 attenuates homologous recombination via destabilizing DNA:RNA hybrids and overcomes PARP inhibitor resistance in cancers
Our study elucidated the mechanism of NAT10-mediated ac4C modification in DSB repair, revealing that targeting NAT10 confers synthetic lethality to PARP inhibition in HCC. Our findings suggest that co-inhibition of NAT10 and PARP1 is an effective novel therapeutic strategy for patients with HCC and have the potential to overcome PARPi resistance.
Authors
- Anliang Xia (ORCID: https://orcid.org/0000-0002-9459-0886)
- Wei‐Guo Zhu (ORCID: https://orcid.org/0000-0001-8385-6581)
- Shihan Liu (ORCID: https://orcid.org/0000-0002-5886-0260)
- Hongda An
- Longpo Geng
- Zhu Xu (ORCID: https://orcid.org/0009-0007-9345-7753)
- Qiang Wang (ORCID: https://orcid.org/0000-0003-0000-9139)
- Jun Zhang (ORCID: https://orcid.org/0000-0002-6523-7573)
- Mingming Zhu (ORCID: https://orcid.org/0000-0002-8097-6892)
- Yuanyuan Yu (ORCID: https://orcid.org/0000-0001-5333-1151)
- Jing Xia (ORCID: https://orcid.org/0000-0003-1792-2063)
- Yiyang Jiang (ORCID: https://orcid.org/0000-0003-4745-9065)
- Beicheng Sun (ORCID: https://orcid.org/0000-0001-7696-703X)
- Junjie Tong (ORCID: https://orcid.org/0009-0009-5715-8961)
Institutions
- Anhui Medical University (CN)
- First Affiliated Hospital of Anhui Medical University (CN)
- Shenzhen University Health Science Center (CN)
Publication Details
- Journal
- Drug Resistance Updates
- Published
- 2025-03-23
- DOI
- https://doi.org/10.1016/j.drup.2025.101241
- Citations
- 8
- Primary Topic
- PARP inhibition in cancer therapy
- Type
- article
- Field-Weighted Citation Impact
- 8.36