Mechanistic insights into SENP1 and OCT4 interaction in promoting drug resistance and stem cell features in colon cancer.

IF 5 2区 生物学 Q2 CELL BIOLOGY
Jun Zou, Jing Chen, Lei Deng, Bangran Xu, Tenghua Yu, Jun Wang, Chongwu He
{"title":"Mechanistic insights into SENP1 and OCT4 interaction in promoting drug resistance and stem cell features in colon cancer.","authors":"Jun Zou, Jing Chen, Lei Deng, Bangran Xu, Tenghua Yu, Jun Wang, Chongwu He","doi":"10.1152/ajpcell.00817.2024","DOIUrl":null,"url":null,"abstract":"<p><p>This study explores the molecular mechanism by which sentrin/SUMO-specific protease 1 (SENP1) promotes cisplatin (Cis) resistance and tumor stem cell characteristics in colon adenocarcinoma (COAD) through deSUMOylation-mediated modification of octamer-binding transcription factor 4 (OCT4). By analyzing single-cell and transcriptome sequencing datasets, we identified key genes and regulatory pathways in both resistant and sensitive COAD cells. Malignant cells were isolated and evaluated for stemness using the infercnv package, and differential genes between Cis-resistant and -sensitive groups were identified. Machine learning algorithms highlighted essential genes, and databases predicted interaction sites between OCT4 and SENP1. In vitro experiments using enriched HCT116 stem cells revealed that SENP1 and OCT4 expression significantly elevated CD44 and CD133 levels, enhancing stemness. Functional assays showed that SENP1's deSUMOylation of OCT4 intensified Cis resistance, migration, and invasion in cisplatin-resistant cell line 116 (Cis-116) cells. In vivo, SENP1 knockdown reduced tumor growth and stem cell markers, whereas OCT4 overexpression escalated tumor metastasis and structural damage. These findings demonstrate that SENP1's modulation of OCT4 is central to COAD's resistance and stem cell properties, offering a novel target for COAD therapy.<b>NEW & NOTEWORTHY</b> This study uncovers the critical role of SENP1 in regulating OCT4 through deSUMOylation, driving Cis resistance and tumor stemness in COAD. Targeting this pathway may provide novel therapeutic strategies for COAD management.</p>","PeriodicalId":7585,"journal":{"name":"American journal of physiology. Cell physiology","volume":" ","pages":"C1260-C1278"},"PeriodicalIF":5.0000,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"American journal of physiology. Cell physiology","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1152/ajpcell.00817.2024","RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/3/10 0:00:00","PubModel":"Epub","JCR":"Q2","JCRName":"CELL BIOLOGY","Score":null,"Total":0}
引用次数: 0

Abstract

This study explores the molecular mechanism by which sentrin/SUMO-specific protease 1 (SENP1) promotes cisplatin (Cis) resistance and tumor stem cell characteristics in colon adenocarcinoma (COAD) through deSUMOylation-mediated modification of octamer-binding transcription factor 4 (OCT4). By analyzing single-cell and transcriptome sequencing datasets, we identified key genes and regulatory pathways in both resistant and sensitive COAD cells. Malignant cells were isolated and evaluated for stemness using the infercnv package, and differential genes between Cis-resistant and -sensitive groups were identified. Machine learning algorithms highlighted essential genes, and databases predicted interaction sites between OCT4 and SENP1. In vitro experiments using enriched HCT116 stem cells revealed that SENP1 and OCT4 expression significantly elevated CD44 and CD133 levels, enhancing stemness. Functional assays showed that SENP1's deSUMOylation of OCT4 intensified Cis resistance, migration, and invasion in cisplatin-resistant cell line 116 (Cis-116) cells. In vivo, SENP1 knockdown reduced tumor growth and stem cell markers, whereas OCT4 overexpression escalated tumor metastasis and structural damage. These findings demonstrate that SENP1's modulation of OCT4 is central to COAD's resistance and stem cell properties, offering a novel target for COAD therapy.NEW & NOTEWORTHY This study uncovers the critical role of SENP1 in regulating OCT4 through deSUMOylation, driving Cis resistance and tumor stemness in COAD. Targeting this pathway may provide novel therapeutic strategies for COAD management.

SENP1和OCT4相互作用促进结肠癌耐药和干细胞特征的机制研究
本研究探讨了SENP1 / sumo特异性蛋白酶1 (SENP1)通过脱苏修饰介导的八聚体结合转录因子4 (OCT4)促进结肠癌(COAD)顺铂(Cis)耐药性和肿瘤干细胞特性的分子机制。通过分析单细胞和转录组测序数据集,我们确定了耐药和敏感COAD细胞的关键基因和调控途径。恶性细胞被分离出来,并使用intercnv包评估其干性,鉴定出顺式耐药组和敏感组之间的差异基因。机器学习算法突出了关键基因,数据库预测了OCT4和SENP1之间的相互作用位点。利用富集的HCT116干细胞进行的体外实验显示,SENP1和OCT4的表达显著提高了CD44和CD133的水平,增强了干细胞的干性。功能分析显示,SENP1对OCT4的去氧化作用增强了顺铂耐药细胞系116 (Cis-116)细胞的顺铂耐药、迁移和侵袭。在体内,SENP1基因敲低可抑制肿瘤生长和干细胞标记物,而OCT4基因过表达会加剧肿瘤转移和结构损伤。这些发现表明,SENP1对OCT4的调节是COAD耐药和干细胞特性的核心,为COAD治疗提供了一个新的靶点。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 求助全文
来源期刊
CiteScore
9.10
自引率
1.80%
发文量
252
审稿时长
1 months
期刊介绍: The American Journal of Physiology-Cell Physiology is dedicated to innovative approaches to the study of cell and molecular physiology. Contributions that use cellular and molecular approaches to shed light on mechanisms of physiological control at higher levels of organization also appear regularly. Manuscripts dealing with the structure and function of cell membranes, contractile systems, cellular organelles, and membrane channels, transporters, and pumps are encouraged. Studies dealing with integrated regulation of cellular function, including mechanisms of signal transduction, development, gene expression, cell-to-cell interactions, and the cell physiology of pathophysiological states, are also eagerly sought. Interdisciplinary studies that apply the approaches of biochemistry, biophysics, molecular biology, morphology, and immunology to the determination of new principles in cell physiology are especially welcome.
×
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:481959085
Book学术官方微信