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PARP4 缺陷通过损害黑色素瘤中的 DNA 损伤修复增强对 ATM 抑制剂的敏感性。

PARP4 deficiency enhances sensitivity to ATM inhibitor by impairing DNA damage repair in melanoma.

作者信息

Li Yuehua, Liu Yu, Ma Jingjing, Yang Yuqi, Yue Qiao, Zhu Guannan, Guo Weinan, Gao Tianwen, Shi Qiong, Li Chunying

机构信息

Department of Dermatology, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, China.

出版信息

Cell Death Discov. 2025 Jan 30;11(1):35. doi: 10.1038/s41420-025-02296-0.

DOI:10.1038/s41420-025-02296-0
PMID:39885134
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11782537/
Abstract

Besides the important pathogenic mechanisms of melanoma, including BRAF-driven and immunosuppressive microenvironment, genomic instability and abnormal DNA double-strand breaks (DSB) repair are significant driving forces for its occurrence and development. This suggests investigating novel therapeutic strategies from the synthetic lethality perspective. Poly (ADP-ribose) polymerase 4 (PARP4) is known to be a member of the PARP protein family. The low expression of PARP4 is significantly associated with defective DSB repair markers and poor prognosis in melanoma. Further research revealed that PARP4 plays a role in DSB repair by regulating the non-homologous end joining (NHEJ) pathway through its involvement in Ku80 mono-ADP-ribosylation. Moreover, from a synthetic lethality perspective, PARP4 expression is associated with ATM inhibitor sensitivity. Overall, our study provides new and valuable insights into the function of PARP4 and melanoma pathogenesis and suggests that ATM inhibitor may be a promising therapeutic approach for treating melanoma with low PARP4 expression.

摘要

除了黑色素瘤的重要致病机制，包括BRAF驱动和免疫抑制微环境外，基因组不稳定性和异常的DNA双链断裂（DSB）修复是其发生和发展的重要驱动力。这表明从合成致死性角度研究新的治疗策略。聚（ADP-核糖）聚合酶4（PARP4）是PARP蛋白家族的成员。PARP4低表达与黑色素瘤中DSB修复标志物缺陷及预后不良显著相关。进一步研究表明，PARP4通过参与Ku80单ADP核糖基化调节非同源末端连接（NHEJ）途径，在DSB修复中发挥作用。此外，从合成致死性角度来看，PARP4表达与ATM抑制剂敏感性相关。总体而言，我们的研究为PARP4的功能和黑色素瘤发病机制提供了新的有价值的见解，并表明ATM抑制剂可能是治疗PARP4低表达黑色素瘤的一种有前景的治疗方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1683/11782537/cc0d19362f85/41420_2025_2296_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1683/11782537/71e0efd25fbd/41420_2025_2296_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1683/11782537/a67f14e4e515/41420_2025_2296_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1683/11782537/991de3ef2bdb/41420_2025_2296_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1683/11782537/5b33f5782eac/41420_2025_2296_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1683/11782537/b3d24bd457d7/41420_2025_2296_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1683/11782537/cc0d19362f85/41420_2025_2296_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1683/11782537/71e0efd25fbd/41420_2025_2296_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1683/11782537/a67f14e4e515/41420_2025_2296_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1683/11782537/991de3ef2bdb/41420_2025_2296_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1683/11782537/5b33f5782eac/41420_2025_2296_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1683/11782537/b3d24bd457d7/41420_2025_2296_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1683/11782537/cc0d19362f85/41420_2025_2296_Fig6_HTML.jpg

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本文引用的文献

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2
Identification of a novel PARP4 gene promoter CpG locus associated with cisplatin chemoresistance.鉴定与顺铂化疗耐药相关的新型 PARP4 基因启动子 CpG 位点。
BMB Rep. 2023 Jun;56(6):347-352. doi: 10.5483/BMBRep.2022-0202.
3
Integrative Genomic Profiling Uncovers Therapeutic Targets of Acral Melanoma in Asian Populations.
整合基因组分析揭示亚洲人群肢端黑色素瘤的治疗靶点。
Clin Cancer Res. 2022 Jun 13;28(12):2690-2703. doi: 10.1158/1078-0432.CCR-21-3344.
4
PARP Power: A Structural Perspective on PARP1, PARP2, and PARP3 in DNA Damage Repair and Nucleosome Remodelling.PARP 力量：PARP1、PARP2 和 PARP3 在 DNA 损伤修复和核小体重塑中的结构视角。
Int J Mol Sci. 2021 May 12;22(10):5112. doi: 10.3390/ijms22105112.
5
Prevalence of Homologous Recombination Pathway Gene Mutations in Melanoma: Rationale for a New Targeted Therapeutic Approach.黑色素瘤中同源重组途径基因突变的流行率：一种新的靶向治疗方法的原理。
J Invest Dermatol. 2021 Aug;141(8):2028-2036.e2. doi: 10.1016/j.jid.2021.01.024. Epub 2021 Feb 19.
6
Cancer Statistics, 2021.癌症统计数据，2021.
CA Cancer J Clin. 2021 Jan;71(1):7-33. doi: 10.3322/caac.21654. Epub 2021 Jan 12.
7
The forefront of ovarian cancer therapy: update on PARP inhibitors.卵巢癌治疗的前沿：PARP 抑制剂的最新进展。
Ann Oncol. 2020 Sep;31(9):1148-1159. doi: 10.1016/j.annonc.2020.06.004. Epub 2020 Jun 20.
8
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10
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