TRIM21 promotes colorectal cancer development through regulating DNA replication by TCF3/MCM2/5 axis.

IF 7 2区生物学 Q1 CELL BIOLOGY

Cell Death Discovery Pub Date : 2025-09-25 DOI:10.1038/s41420-025-02722-3

Xintian Zhang, Han Yao, Yichao Hou, Kun Zhou, Yu Liang, Lidan Hou, Xingming Zhang, Wenfeng Wang, Leilei Du, Mengfei Yao, Jianhua Wang, Xiangjun Meng

{"title":"TRIM21 promotes colorectal cancer development through regulating DNA replication by TCF3/MCM2/5 axis.","authors":"Xintian Zhang, Han Yao, Yichao Hou, Kun Zhou, Yu Liang, Lidan Hou, Xingming Zhang, Wenfeng Wang, Leilei Du, Mengfei Yao, Jianhua Wang, Xiangjun Meng","doi":"10.1038/s41420-025-02722-3","DOIUrl":null,"url":null,"abstract":"<p><p>Disrupting DNA replication has been employed for treating cancers. In the present study, we found that Tripartite motif containing 21 (TRIM21) was highly expressed in colorectal cancer (CRC) and could be valuable for predicting the prognosis of CRC patients. Further study demonstrated that TRIM21 positively regulated the expression of MCM2 and MCM5, DNA replication and proliferation of CRC cells both in vitro and in vivo. In addition, TRIM21 knockdown inhibited both replication initiation and velocity, and increased the chemosensitivity of CRC cells to 5-FU and SN-38. Our study also revealed that DNA replication inhibition following TRIM21 knockdown could not be restored by cell cycle checkpoint kinase inhibitors, but partially by Transcription Factor 3 (TCF3) knockdown. TCF3 directly suppressed MCM2 and MCM5 transcription, inhibiting DNA replication. In summary, TRIM21 could influence tumor development and chemosensitivity to replication inhibitors by regulating DNA replication through the TCF3/MCM2/5 axis, suggesting a promising potential for CRC in the clinic.</p>","PeriodicalId":9735,"journal":{"name":"Cell Death Discovery","volume":"11 1","pages":"422"},"PeriodicalIF":7.0000,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12462522/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cell Death Discovery","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1038/s41420-025-02722-3","RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CELL BIOLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

Disrupting DNA replication has been employed for treating cancers. In the present study, we found that Tripartite motif containing 21 (TRIM21) was highly expressed in colorectal cancer (CRC) and could be valuable for predicting the prognosis of CRC patients. Further study demonstrated that TRIM21 positively regulated the expression of MCM2 and MCM5, DNA replication and proliferation of CRC cells both in vitro and in vivo. In addition, TRIM21 knockdown inhibited both replication initiation and velocity, and increased the chemosensitivity of CRC cells to 5-FU and SN-38. Our study also revealed that DNA replication inhibition following TRIM21 knockdown could not be restored by cell cycle checkpoint kinase inhibitors, but partially by Transcription Factor 3 (TCF3) knockdown. TCF3 directly suppressed MCM2 and MCM5 transcription, inhibiting DNA replication. In summary, TRIM21 could influence tumor development and chemosensitivity to replication inhibitors by regulating DNA replication through the TCF3/MCM2/5 axis, suggesting a promising potential for CRC in the clinic.

查看原文本刊更多论文

TRIM21通过TCF3/MCM2/5轴调控DNA复制促进结直肠癌的发展。

破坏DNA复制已被用于治疗癌症。在本研究中，我们发现Tripartite motif containing 21 （TRIM21）在结直肠癌（CRC）中高表达，对预测结直肠癌患者的预后具有重要价值。进一步研究表明，TRIM21在体外和体内均对CRC细胞MCM2和MCM5的表达、DNA复制和增殖具有正向调节作用。此外，TRIM21敲低抑制了CRC细胞的复制起始和复制速度，增加了CRC细胞对5-FU和SN-38的化学敏感性。我们的研究还表明，细胞周期检查点激酶抑制剂不能恢复TRIM21敲低后的DNA复制抑制，但部分可以通过敲低转录因子3 （TCF3）来恢复。TCF3直接抑制MCM2和MCM5的转录，抑制DNA复制。综上所述，TRIM21可能通过TCF3/MCM2/5轴调节DNA复制，从而影响肿瘤的发展和对复制抑制剂的化学敏感性，这表明TRIM21在临床治疗CRC方面具有广阔的潜力。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Cell Death Discovery Biochemistry, Genetics and Molecular Biology-Cell Biology

CiteScore

8.30

自引率

1.40%

发文量

468

审稿时长

9 weeks

期刊介绍： Cell Death Discovery is a multidisciplinary, international, online-only, open access journal, dedicated to publishing research at the intersection of medicine with biochemistry, pharmacology, immunology, cell biology and cell death, provided it is scientifically sound. The unrestricted access to research findings in Cell Death Discovery will foster a dynamic and highly productive dialogue between basic scientists and clinicians, as well as researchers in industry with a focus on cancer, neurobiology and inflammation research. As an official journal of the Cell Death Differentiation Association (ADMC), Cell Death Discovery will build upon the success of Cell Death & Differentiation and Cell Death & Disease in publishing important peer-reviewed original research, timely reviews and editorial commentary. Cell Death Discovery is committed to increasing the reproducibility of research. To this end, in conjunction with its sister journals Cell Death & Differentiation and Cell Death & Disease, Cell Death Discovery provides a unique forum for scientists as well as clinicians and members of the pharmaceutical and biotechnical industry. It is committed to the rapid publication of high quality original papers that relate to these subjects, together with topical, usually solicited, reviews, editorial correspondence and occasional commentaries on controversial and scientifically informative issues.