液-液相分离的ZHX2通过诱导SLC3A2对DLBCL细胞有保护作用

IF 13.4 1区 医学 Q1 HEMATOLOGY
Juan Zhang, Dongmei Wang, Mengfan Luan, Xiaomin Liu, Nana Wang, Xue Sheng, Shuying Li, Boya Li, Tao Sun, Daoxin Ma, Jingjing Ye, Fei Lu, Chunyan Ji
{"title":"液-液相分离的ZHX2通过诱导SLC3A2对DLBCL细胞有保护作用","authors":"Juan Zhang, Dongmei Wang, Mengfan Luan, Xiaomin Liu, Nana Wang, Xue Sheng, Shuying Li, Boya Li, Tao Sun, Daoxin Ma, Jingjing Ye, Fei Lu, Chunyan Ji","doi":"10.1038/s41375-025-02718-z","DOIUrl":null,"url":null,"abstract":"Diffuse large B-cell lymphoma (DLBCL), the most common B-cell non-Hodgkin lymphoma (B-NHL), is characterized by strong aggression, high heterogeneity, and poor prognosis. Consequently, there is an urgent need to identify crucial therapeutic targets. Here, we found that the transcription factor zinc-finger and homeobox 2 (ZHX2) was highly expressed in DLBCL. Subsequently, ZHX2 was proven to be critical for promoting DLBCL cell proliferation by inhibiting ferroptosis. Mechanistically, ZHX2 bound to the promoter region of the solute carrier family 3-member 2 (SLC3A2) gene through liquid-liquid phase separation (LLPS) and activated its function to negatively regulate ferroptosis. Furthermore, we constructed lipid nanoparticles ZHX2-siRNA@LNP targeting DLBCL, which effectively inhibited the growth of the tumors in vivo. In summary, our study indicated that the LLPS of ZHX2 protected DLBCL against ferroptosis through induction of SLC3A2, and disturbing it with ZHX2-siRNA@LNP could significantly repress DLBCL, providing a promising therapeutic strategy for DLBCL.","PeriodicalId":18109,"journal":{"name":"Leukemia","volume":"39 10","pages":"2442-2451"},"PeriodicalIF":13.4000,"publicationDate":"2025-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41375-025-02718-z.pdf","citationCount":"0","resultStr":"{\"title\":\"Liquid-liquid phase separation of ZHX2 protects DLBCL cells against ferroptosis through induction of SLC3A2\",\"authors\":\"Juan Zhang, Dongmei Wang, Mengfan Luan, Xiaomin Liu, Nana Wang, Xue Sheng, Shuying Li, Boya Li, Tao Sun, Daoxin Ma, Jingjing Ye, Fei Lu, Chunyan Ji\",\"doi\":\"10.1038/s41375-025-02718-z\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"Diffuse large B-cell lymphoma (DLBCL), the most common B-cell non-Hodgkin lymphoma (B-NHL), is characterized by strong aggression, high heterogeneity, and poor prognosis. Consequently, there is an urgent need to identify crucial therapeutic targets. Here, we found that the transcription factor zinc-finger and homeobox 2 (ZHX2) was highly expressed in DLBCL. Subsequently, ZHX2 was proven to be critical for promoting DLBCL cell proliferation by inhibiting ferroptosis. Mechanistically, ZHX2 bound to the promoter region of the solute carrier family 3-member 2 (SLC3A2) gene through liquid-liquid phase separation (LLPS) and activated its function to negatively regulate ferroptosis. Furthermore, we constructed lipid nanoparticles ZHX2-siRNA@LNP targeting DLBCL, which effectively inhibited the growth of the tumors in vivo. In summary, our study indicated that the LLPS of ZHX2 protected DLBCL against ferroptosis through induction of SLC3A2, and disturbing it with ZHX2-siRNA@LNP could significantly repress DLBCL, providing a promising therapeutic strategy for DLBCL.\",\"PeriodicalId\":18109,\"journal\":{\"name\":\"Leukemia\",\"volume\":\"39 10\",\"pages\":\"2442-2451\"},\"PeriodicalIF\":13.4000,\"publicationDate\":\"2025-07-29\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.nature.comhttps://www.nature.com/articles/s41375-025-02718-z.pdf\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Leukemia\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.nature.com/articles/s41375-025-02718-z\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"HEMATOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Leukemia","FirstCategoryId":"3","ListUrlMain":"https://www.nature.com/articles/s41375-025-02718-z","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"HEMATOLOGY","Score":null,"Total":0}
引用次数: 0

摘要

弥漫性大b细胞淋巴瘤(DLBCL)是最常见的b细胞非霍奇金淋巴瘤(B-NHL),具有侵袭性强、异质性高、预后差的特点。因此,迫切需要确定关键的治疗靶点。我们发现转录因子zn -finger and homeobox 2 (ZHX2)在DLBCL中高表达。随后,ZHX2被证明通过抑制铁下垂促进DLBCL细胞增殖。机制上,ZHX2通过液-液相分离(LLPS)结合到溶质载体家族3-member 2 (SLC3A2)基因的启动子区,激活其负调控铁凋亡的功能。此外,我们构建了靶向DLBCL的脂质纳米颗粒ZHX2-siRNA@LNP,在体内有效抑制了肿瘤的生长。综上所述,我们的研究表明,ZHX2的LLPS通过诱导SLC3A2来保护DLBCL抗铁沉,而ZHX2-siRNA@LNP对其进行干扰可以显著抑制DLBCL,为DLBCL提供了一种很有前景的治疗策略。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Liquid-liquid phase separation of ZHX2 protects DLBCL cells against ferroptosis through induction of SLC3A2

Liquid-liquid phase separation of ZHX2 protects DLBCL cells against ferroptosis through induction of SLC3A2

Liquid-liquid phase separation of ZHX2 protects DLBCL cells against ferroptosis through induction of SLC3A2
Diffuse large B-cell lymphoma (DLBCL), the most common B-cell non-Hodgkin lymphoma (B-NHL), is characterized by strong aggression, high heterogeneity, and poor prognosis. Consequently, there is an urgent need to identify crucial therapeutic targets. Here, we found that the transcription factor zinc-finger and homeobox 2 (ZHX2) was highly expressed in DLBCL. Subsequently, ZHX2 was proven to be critical for promoting DLBCL cell proliferation by inhibiting ferroptosis. Mechanistically, ZHX2 bound to the promoter region of the solute carrier family 3-member 2 (SLC3A2) gene through liquid-liquid phase separation (LLPS) and activated its function to negatively regulate ferroptosis. Furthermore, we constructed lipid nanoparticles ZHX2-siRNA@LNP targeting DLBCL, which effectively inhibited the growth of the tumors in vivo. In summary, our study indicated that the LLPS of ZHX2 protected DLBCL against ferroptosis through induction of SLC3A2, and disturbing it with ZHX2-siRNA@LNP could significantly repress DLBCL, providing a promising therapeutic strategy for DLBCL.
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
Leukemia
Leukemia 医学-血液学
CiteScore
18.10
自引率
3.50%
发文量
270
审稿时长
3-6 weeks
期刊介绍: Title: Leukemia Journal Overview: Publishes high-quality, peer-reviewed research Covers all aspects of research and treatment of leukemia and allied diseases Includes studies of normal hemopoiesis due to comparative relevance Topics of Interest: Oncogenes Growth factors Stem cells Leukemia genomics Cell cycle Signal transduction Molecular targets for therapy And more Content Types: Original research articles Reviews Letters Correspondence Comments elaborating on significant advances and covering topical issues
×
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
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
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 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:604180095
Book学术官方微信