核糖核酸酶 ZC3H12A 是小细胞肺癌细胞 DNA 损伤后自残 DNA 断裂的必要条件

IF 6.6 2区 医学 Q1 Medicine Cellular Oncology Pub Date : 2024-03-18 DOI:10.1007/s13402-024-00941-x
Mingjun Lu, Qing Gao, Renjing Jin, Meng Gu, Ziyu Wang, Xiaobo Li, Weiying Li, Jinghui Wang, Teng Ma
{"title":"核糖核酸酶 ZC3H12A 是小细胞肺癌细胞 DNA 损伤后自残 DNA 断裂的必要条件","authors":"Mingjun Lu, Qing Gao, Renjing Jin, Meng Gu, Ziyu Wang, Xiaobo Li, Weiying Li, Jinghui Wang, Teng Ma","doi":"10.1007/s13402-024-00941-x","DOIUrl":null,"url":null,"abstract":"<p>Radiotherapy is the first line treatment for small cell lung cancer (SCLC); However, radio-resistance accompanies with the treatment and hampers the prognosis for SCLC patients. The underlying mechanisms remains elusive. Here we discovered that self-inflicted DNA breaks exist in SCLC cells after radiation. Moreover, using nuclease siRNA screening combined with high-content ArrayScan™ cell analyzer, we identified that Ribonuclease ZC3H12A is required for the self-inflicted DNA breaks after radiation and for SCLC cell survival after DNA damage. ZC3H12A expression was increased in response to DNA damage and when ZC3H12A was knocked down, the DNA repair ability of the cells was impaired, as evidenced by decreased expression of the DNA damage repair protein BRCA1, and increased γH2AX at DNA damage sites. Colony formation assay demonstrates that ZC3H12A knocked down sensitized small cell lung cancer radiotherapy. Therefore, the Ribonuclease ZC3H12A regulates endogenous secondary breaks in small cell lung cancer and affects DNA damage repair. ZC3H12A may act as an important radiotherapy target in small cell lung cancer.</p>","PeriodicalId":9690,"journal":{"name":"Cellular Oncology","volume":null,"pages":null},"PeriodicalIF":6.6000,"publicationDate":"2024-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"The Ribonuclease ZC3H12A is required for self-inflicted DNA breaks after DNA damage in small cell lung cancer cells\",\"authors\":\"Mingjun Lu, Qing Gao, Renjing Jin, Meng Gu, Ziyu Wang, Xiaobo Li, Weiying Li, Jinghui Wang, Teng Ma\",\"doi\":\"10.1007/s13402-024-00941-x\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p>Radiotherapy is the first line treatment for small cell lung cancer (SCLC); However, radio-resistance accompanies with the treatment and hampers the prognosis for SCLC patients. The underlying mechanisms remains elusive. Here we discovered that self-inflicted DNA breaks exist in SCLC cells after radiation. Moreover, using nuclease siRNA screening combined with high-content ArrayScan™ cell analyzer, we identified that Ribonuclease ZC3H12A is required for the self-inflicted DNA breaks after radiation and for SCLC cell survival after DNA damage. ZC3H12A expression was increased in response to DNA damage and when ZC3H12A was knocked down, the DNA repair ability of the cells was impaired, as evidenced by decreased expression of the DNA damage repair protein BRCA1, and increased γH2AX at DNA damage sites. Colony formation assay demonstrates that ZC3H12A knocked down sensitized small cell lung cancer radiotherapy. Therefore, the Ribonuclease ZC3H12A regulates endogenous secondary breaks in small cell lung cancer and affects DNA damage repair. ZC3H12A may act as an important radiotherapy target in small cell lung cancer.</p>\",\"PeriodicalId\":9690,\"journal\":{\"name\":\"Cellular Oncology\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":6.6000,\"publicationDate\":\"2024-03-18\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Cellular Oncology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1007/s13402-024-00941-x\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"Medicine\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cellular Oncology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s13402-024-00941-x","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"Medicine","Score":null,"Total":0}
引用次数: 0

摘要

放疗是治疗小细胞肺癌(SCLC)的一线疗法;然而,放射抗药性伴随着放疗,阻碍了小细胞肺癌患者的预后。其潜在的机制仍然难以捉摸。在这里,我们发现在辐射后,SCLC 细胞中存在自我损伤的 DNA 断裂。此外,通过核酸酶 siRNA 筛选结合高含量 ArrayScan™ 细胞分析仪,我们发现核糖核酸酶 ZC3H12A 是辐射后自残 DNA 断裂和 SCLC 细胞在 DNA 损伤后存活的必要条件。ZC3H12A 的表达在 DNA 损伤时增加,当 ZC3H12A 被敲除时,细胞的 DNA 修复能力受损,表现为 DNA 损伤修复蛋白 BRCA1 的表达减少,DNA 损伤位点的 γH2AX 增加。集落形成试验表明,ZC3H12A 基因敲除可使小细胞肺癌放疗增敏。因此,核糖核酸酶 ZC3H12A 可调节小细胞肺癌的内源性二次断裂并影响 DNA 损伤修复。ZC3H12A可能是小细胞肺癌放疗的一个重要靶点。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

摘要图片

查看原文
分享 分享
微信好友 朋友圈 QQ好友 复制链接
本刊更多论文
The Ribonuclease ZC3H12A is required for self-inflicted DNA breaks after DNA damage in small cell lung cancer cells

Radiotherapy is the first line treatment for small cell lung cancer (SCLC); However, radio-resistance accompanies with the treatment and hampers the prognosis for SCLC patients. The underlying mechanisms remains elusive. Here we discovered that self-inflicted DNA breaks exist in SCLC cells after radiation. Moreover, using nuclease siRNA screening combined with high-content ArrayScan™ cell analyzer, we identified that Ribonuclease ZC3H12A is required for the self-inflicted DNA breaks after radiation and for SCLC cell survival after DNA damage. ZC3H12A expression was increased in response to DNA damage and when ZC3H12A was knocked down, the DNA repair ability of the cells was impaired, as evidenced by decreased expression of the DNA damage repair protein BRCA1, and increased γH2AX at DNA damage sites. Colony formation assay demonstrates that ZC3H12A knocked down sensitized small cell lung cancer radiotherapy. Therefore, the Ribonuclease ZC3H12A regulates endogenous secondary breaks in small cell lung cancer and affects DNA damage repair. ZC3H12A may act as an important radiotherapy target in small cell lung cancer.

求助全文
通过发布文献求助,成功后即可免费获取论文全文。 去求助
来源期刊
Cellular Oncology
Cellular Oncology Biochemistry, Genetics and Molecular Biology-Cancer Research
CiteScore
10.40
自引率
1.50%
发文量
0
审稿时长
16 weeks
期刊介绍: The Official Journal of the International Society for Cellular Oncology Focuses on translational research Addresses the conversion of cell biology to clinical applications Cellular Oncology publishes scientific contributions from various biomedical and clinical disciplines involved in basic and translational cancer research on the cell and tissue level, technical and bioinformatics developments in this area, and clinical applications. This includes a variety of fields like genome technology, micro-arrays and other high-throughput techniques, genomic instability, SNP, DNA methylation, signaling pathways, DNA organization, (sub)microscopic imaging, proteomics, bioinformatics, functional effects of genomics, drug design and development, molecular diagnostics and targeted cancer therapies, genotype-phenotype interactions. A major goal is to translate the latest developments in these fields from the research laboratory into routine patient management. To this end Cellular Oncology forms a platform of scientific information exchange between molecular biologists and geneticists, technical developers, pathologists, (medical) oncologists and other clinicians involved in the management of cancer patients. In vitro studies are preferentially supported by validations in tumor tissue with clinicopathological associations.
期刊最新文献
Cell death in glioblastoma and the central nervous system. SUMOylation regulates the aggressiveness of breast cancer-associated fibroblasts. Retraction Note: The autocrine glycosylated-GREM1 interacts with TGFB1 to suppress TGFβ/BMP/SMAD-mediated EMT partially by inhibiting MYL9 transactivation in urinary carcinoma. USP28 promotes tumor progression and glycolysis by stabilizing PKM2/Hif1-α in cholangiocarcinoma. BCAT1 contributes to the development of TKI-resistant CML.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
已复制链接
已复制链接
快去分享给好友吧!
我知道了
×
扫码分享
扫码分享
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1