• 文献检索
  • 文档翻译
  • 深度研究
  • 学术资讯
  • Suppr Zotero 插件Zotero 插件
  • 邀请有礼
  • 套餐&价格
  • 历史记录
应用&插件
Suppr Zotero 插件Zotero 插件浏览器插件Mac 客户端Windows 客户端微信小程序
定价
高级版会员购买积分包购买API积分包
服务
文献检索文档翻译深度研究API 文档MCP 服务
关于我们
关于 Suppr公司介绍联系我们用户协议隐私条款
关注我们

Suppr 超能文献

核心技术专利：CN118964589B侵权必究
粤ICP备2023148730 号-1Suppr @ 2026

文献检索

告别复杂PubMed语法，用中文像聊天一样搜索，搜遍4000万医学文献。AI智能推荐，让科研检索更轻松。

立即免费搜索

文件翻译

保留排版，准确专业，支持PDF/Word/PPT等文件格式，支持 12+语言互译。

免费翻译文档

深度研究

AI帮你快速写综述，25分钟生成高质量综述，智能提取关键信息，辅助科研写作。

立即免费体验

一种RNA解旋酶DHX33抑制剂通过诱导癌细胞铁死亡显示出广泛的抗癌活性。

An RNA Helicase DHX33 Inhibitor Shows Broad Anticancer Activity via Inducing Ferroptosis in Cancer Cells.

作者信息

Tang Xiyu, Deng Yuanlian, Liang Yingying, Liao Deqing, Wen Fuyu, Zhang Yandong

机构信息

Shenzhen KeYe Life Technologies Co., Ltd, Shenzhen, Guangdong 518155, China.

出版信息

ACS Omega. 2024 Jun 17;9(26):28372-28384. doi: 10.1021/acsomega.4c02265. eCollection 2024 Jul 2.

DOI:10.1021/acsomega.4c02265
PMID:38973855
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11223218/
Abstract

RNA helicase DHX33 has been identified as a critical factor promoting cancer development. In the present study, a previously developed small molecule inhibitor for DHX33, KY386, was found to robustly kill cancer cells via a new path, the ferroptosis pathway. Mechanistically, DHX33 promotes the expression of critical players in lipid metabolism including FADS1, FADS2, and SCD1 genes, thereby sensitizing cancer cells to ferroptosis mediated cell death. Our study reveals a novel mechanism of DHX33 in promoting tumorigenesis and highlights that pharmacological targeting DHX33 can be a feasible option in human cancers. Normally differentiated cells are insensitive to DHX33 inhibition, and DHX33 inhibitors have little cellular toxicity in vitro and in vivo. Our studies demonstrated that DHX33 inhibitors can be promising anticancer agents with great potential for cancer treatment.

摘要

RNA解旋酶DHX33已被确定为促进癌症发展的关键因素。在本研究中，一种先前开发的针对DHX33的小分子抑制剂KY386被发现可通过一种新途径——铁死亡途径强力杀死癌细胞。从机制上讲，DHX33促进脂质代谢中关键因子的表达，包括FADS1、FADS2和SCD1基因，从而使癌细胞对铁死亡介导的细胞死亡敏感。我们的研究揭示了DHX33促进肿瘤发生的新机制，并强调对DHX33进行药理学靶向可能是人类癌症的一种可行选择。正常分化的细胞对DHX33抑制不敏感，并且DHX33抑制剂在体外和体内几乎没有细胞毒性。我们的研究表明，DHX33抑制剂有望成为具有巨大癌症治疗潜力的抗癌药物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7db9/11223218/a8b9a1fb3a24/ao4c02265_0007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7db9/11223218/16e5c6dc0b4e/ao4c02265_0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7db9/11223218/fcde242641bd/ao4c02265_0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7db9/11223218/d88940c80085/ao4c02265_0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7db9/11223218/beae95910d0b/ao4c02265_0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7db9/11223218/0fc5f9dbee4c/ao4c02265_0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7db9/11223218/0dcca876074c/ao4c02265_0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7db9/11223218/a8b9a1fb3a24/ao4c02265_0007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7db9/11223218/16e5c6dc0b4e/ao4c02265_0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7db9/11223218/fcde242641bd/ao4c02265_0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7db9/11223218/d88940c80085/ao4c02265_0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7db9/11223218/beae95910d0b/ao4c02265_0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7db9/11223218/0fc5f9dbee4c/ao4c02265_0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7db9/11223218/0dcca876074c/ao4c02265_0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7db9/11223218/a8b9a1fb3a24/ao4c02265_0007.jpg

相似文献

1
An RNA Helicase DHX33 Inhibitor Shows Broad Anticancer Activity via Inducing Ferroptosis in Cancer Cells.一种RNA解旋酶DHX33抑制剂通过诱导癌细胞铁死亡显示出广泛的抗癌活性。
ACS Omega. 2024 Jun 17;9(26):28372-28384. doi: 10.1021/acsomega.4c02265. eCollection 2024 Jul 2.
2
Development of small molecule inhibitors targeting RNA helicase DHX33 as anti-cancer agents.开发针对 RNA 解旋酶 DHX33 的小分子抑制剂作为抗癌药物。
Bioorg Med Chem Lett. 2023 Nov 15;96:129505. doi: 10.1016/j.bmcl.2023.129505. Epub 2023 Oct 12.
3
Targeting RNA helicase DHX33 blocks Ras-driven lung tumorigenesis in vivo.靶向 RNA 解旋酶 DHX33 阻断体内 Ras 驱动的肺肿瘤发生。
Cancer Sci. 2020 Oct;111(10):3564-3575. doi: 10.1111/cas.14601. Epub 2020 Aug 24.
4
RNA helicase DHX33 regulates HMGB family genes in human cancer cells.RNA 解旋酶 DHX33 调节人癌细胞中的 HMGB 家族基因。
Cell Signal. 2023 Oct;110:110832. doi: 10.1016/j.cellsig.2023.110832. Epub 2023 Aug 4.
5
DHX33 promotes colon cancer development downstream of Wnt signaling.DHX33 促进 Wnt 信号下游的结肠癌发生。
Gene. 2020 Apr 20;735:144402. doi: 10.1016/j.gene.2020.144402. Epub 2020 Jan 28.
6
The RNA helicase DHX33 is required for cancer cell proliferation in human glioblastoma and confers resistance to PI3K/mTOR inhibition.RNA 解旋酶 DHX33 是人神经胶质瘤细胞增殖所必需的，并且赋予了对 PI3K/mTOR 抑制的抗性。
Cell Signal. 2019 Feb;54:170-178. doi: 10.1016/j.cellsig.2018.12.005. Epub 2018 Dec 12.
7
Recombinant DHX33 Protein Possesses Dual DNA/RNA Helicase Activity.重组 DHX33 蛋白具有双重 DNA/RNA 解旋酶活性。
Biochemistry. 2019 Jan 29;58(4):250-258. doi: 10.1021/acs.biochem.8b00166. Epub 2018 Jun 13.
8
GSK-3β phosphorylation of DHX33 leads to its ubiquitination mediated protein degradation.GSK-3β 对 DHX33 的磷酸化导致其泛素化介导的蛋白降解。
Cell Signal. 2023 Jan;101:110526. doi: 10.1016/j.cellsig.2022.110526. Epub 2022 Nov 18.
9
DHX33 Interacts with AP-2β To Regulate Gene Expression and Promote Cancer Cell Survival.DHX33 与 AP-2β 相互作用以调节基因表达并促进癌细胞存活。
Mol Cell Biol. 2019 Aug 12;39(17). doi: 10.1128/MCB.00017-19. Print 2019 Sep 1.
10
DHX33 mediates p53 to regulate mevalonate pathway gene transcription in human cancers.DHX33介导p53以调控人类癌症中甲羟戊酸途径基因的转录。
Biochim Biophys Acta Gen Subj. 2024 Mar;1868(3):130547. doi: 10.1016/j.bbagen.2023.130547. Epub 2023 Dec 22.

本文引用的文献

1
Dysregulated palmitic acid metabolism promotes the formation of renal calcium-oxalate stones through ferroptosis induced by polyunsaturated fatty acids/phosphatidic acid.代谢失调的棕榈酸通过多不饱和脂肪酸/磷酸脂诱导的铁死亡促进肾草酸钙结石的形成。
Cell Mol Life Sci. 2024 Feb 12;81(1):85. doi: 10.1007/s00018-024-05145-y.
2
DHX33 mediates p53 to regulate mevalonate pathway gene transcription in human cancers.DHX33介导p53以调控人类癌症中甲羟戊酸途径基因的转录。
Biochim Biophys Acta Gen Subj. 2024 Mar;1868(3):130547. doi: 10.1016/j.bbagen.2023.130547. Epub 2023 Dec 22.
3
Development of small molecule inhibitors targeting RNA helicase DHX33 as anti-cancer agents.
开发针对 RNA 解旋酶 DHX33 的小分子抑制剂作为抗癌药物。
Bioorg Med Chem Lett. 2023 Nov 15;96:129505. doi: 10.1016/j.bmcl.2023.129505. Epub 2023 Oct 12.
4
RNA helicase DHX33 regulates HMGB family genes in human cancer cells.RNA 解旋酶 DHX33 调节人癌细胞中的 HMGB 家族基因。
Cell Signal. 2023 Oct;110:110832. doi: 10.1016/j.cellsig.2023.110832. Epub 2023 Aug 4.
5
Cellular functions of eukaryotic RNA helicases and their links to human diseases.真核 RNA 解旋酶的细胞功能及其与人类疾病的关联。
Nat Rev Mol Cell Biol. 2023 Oct;24(10):749-769. doi: 10.1038/s41580-023-00628-5. Epub 2023 Jul 20.
6
Ferroptosis-related molecular patterns reveal immune escape, inflammatory development and lipid metabolism characteristics of the tumor microenvironment in acute myeloid leukemia.铁死亡相关分子模式揭示急性髓系白血病肿瘤微环境的免疫逃逸、炎症发展及脂质代谢特征
Front Oncol. 2022 Nov 28;12:888570. doi: 10.3389/fonc.2022.888570. eCollection 2022.
7
Identification of SLC3A2 as a Potential Therapeutic Target of Osteoarthritis Involved in Ferroptosis by Integrating Bioinformatics, Clinical Factors and Experiments.整合生物信息学、临床因素和实验鉴定 SLC3A2 为铁死亡参与的骨关节炎的潜在治疗靶点。
Cells. 2022 Oct 30;11(21):3430. doi: 10.3390/cells11213430.
8
Measuring the impact of cofactors on RNA helicase activities.测量辅因子对 RNA 解旋酶活性的影响。
Methods. 2022 Aug;204:376-385. doi: 10.1016/j.ymeth.2022.04.005. Epub 2022 Apr 14.
9
DEAD-Box RNA Helicases in Cell Cycle Control and Clinical Therapy.细胞周期调控与临床治疗中的 DEAD-Box RNA 解旋酶。
Cells. 2021 Jun 18;10(6):1540. doi: 10.3390/cells10061540.
10
Regulation of RNA helicase activity: principles and examples.RNA 解旋酶活性的调控：原理与实例。
Biol Chem. 2021 Feb 15;402(5):529-559. doi: 10.1515/hsz-2020-0362. Print 2021 Apr 27.