Sentrin/ sumo特异性蛋白酶1通过介导yes相关蛋白的去umo化参与黑色素瘤的耐药。

IF 1.4 4区 医学 Q3 ALLERGY
Postepy Dermatologii I Alergologii Pub Date : 2025-08-11 eCollection Date: 2025-08-01 DOI:10.5114/ada.2025.153499
Bei Zhao, Yinghua Liu, Xuemei Tang, Shi Cheng
{"title":"Sentrin/ sumo特异性蛋白酶1通过介导yes相关蛋白的去umo化参与黑色素瘤的耐药。","authors":"Bei Zhao, Yinghua Liu, Xuemei Tang, Shi Cheng","doi":"10.5114/ada.2025.153499","DOIUrl":null,"url":null,"abstract":"<p><strong>Introduction: </strong>The effectiveness of chemotherapy in treating melanoma is limited due to drug resistance. Previous studies have shown that SENP1 (Sentrin/SUMO-specific protease 1) is related to the tumour hypoxic microenvironment, tumorigenesis and metastasis.</p><p><strong>Aim: </strong>This study aimed to investigate its roles in drug resistance of melanoma.</p><p><strong>Material and methods: </strong>Originally, a concentration of 2 μg/ml dacarbazine (DTIC) was employed in the treatment of A375 and M14 cell lines for a duration of 24 h. Subsequently, the cells were transferred to fresh medium and allowed to proliferate until reaching 80% of their maximum density. This treatment cycle was then repeated for a total of 10 days, following which the DTIC concentration was doubled. The establishment of drug-resistant cell lines for both A375 and M14 occurred after 8 months of sustained and continuous treatment. The expression level of SENP1 was monitored monthly using real-time reverse transcriptase-polymerase chain reaction (RT-qPCR), with a fold change above 1.5 compared to the untreated condition considered as significant.</p><p><strong>Results: </strong>Finally, the study found that SENP1 was up-regulated by about 2.2-1.7 times in the drug-resistant cells. In addition, overexpression of SENP1 in normal A375 cells improved cell viability against DTIC. The study also found that Yes-associated protein (YAP) could form protein condensates in the cytoplasm while its expression was enhanced by SENP1-mediated deSUMOylation.</p><p><strong>Conclusions: </strong>This study suggests that there is a positive correlation between the ubiquitin-specific protease SENP1 and drug resistance in melanoma. Its up-regulation may lead to changes in the deSUMOylation of YAP, activate the Hippo signalling pathway, and increase the resistance of melanoma to DTIC.</p>","PeriodicalId":54595,"journal":{"name":"Postepy Dermatologii I Alergologii","volume":"42 4","pages":"398-406"},"PeriodicalIF":1.4000,"publicationDate":"2025-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12458072/pdf/","citationCount":"0","resultStr":"{\"title\":\"Sentrin/SUMO-specific protease 1 contributes to drug resistance in melanoma by mediating the deSUMOylation of Yes-associated protein.\",\"authors\":\"Bei Zhao, Yinghua Liu, Xuemei Tang, Shi Cheng\",\"doi\":\"10.5114/ada.2025.153499\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Introduction: </strong>The effectiveness of chemotherapy in treating melanoma is limited due to drug resistance. Previous studies have shown that SENP1 (Sentrin/SUMO-specific protease 1) is related to the tumour hypoxic microenvironment, tumorigenesis and metastasis.</p><p><strong>Aim: </strong>This study aimed to investigate its roles in drug resistance of melanoma.</p><p><strong>Material and methods: </strong>Originally, a concentration of 2 μg/ml dacarbazine (DTIC) was employed in the treatment of A375 and M14 cell lines for a duration of 24 h. Subsequently, the cells were transferred to fresh medium and allowed to proliferate until reaching 80% of their maximum density. This treatment cycle was then repeated for a total of 10 days, following which the DTIC concentration was doubled. The establishment of drug-resistant cell lines for both A375 and M14 occurred after 8 months of sustained and continuous treatment. The expression level of SENP1 was monitored monthly using real-time reverse transcriptase-polymerase chain reaction (RT-qPCR), with a fold change above 1.5 compared to the untreated condition considered as significant.</p><p><strong>Results: </strong>Finally, the study found that SENP1 was up-regulated by about 2.2-1.7 times in the drug-resistant cells. In addition, overexpression of SENP1 in normal A375 cells improved cell viability against DTIC. The study also found that Yes-associated protein (YAP) could form protein condensates in the cytoplasm while its expression was enhanced by SENP1-mediated deSUMOylation.</p><p><strong>Conclusions: </strong>This study suggests that there is a positive correlation between the ubiquitin-specific protease SENP1 and drug resistance in melanoma. Its up-regulation may lead to changes in the deSUMOylation of YAP, activate the Hippo signalling pathway, and increase the resistance of melanoma to DTIC.</p>\",\"PeriodicalId\":54595,\"journal\":{\"name\":\"Postepy Dermatologii I Alergologii\",\"volume\":\"42 4\",\"pages\":\"398-406\"},\"PeriodicalIF\":1.4000,\"publicationDate\":\"2025-08-11\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12458072/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Postepy Dermatologii I Alergologii\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.5114/ada.2025.153499\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2025/8/1 0:00:00\",\"PubModel\":\"eCollection\",\"JCR\":\"Q3\",\"JCRName\":\"ALLERGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Postepy Dermatologii I Alergologii","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.5114/ada.2025.153499","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/8/1 0:00:00","PubModel":"eCollection","JCR":"Q3","JCRName":"ALLERGY","Score":null,"Total":0}
引用次数: 0

摘要

由于耐药,化疗治疗黑色素瘤的有效性受到限制。既往研究表明,SENP1 (Sentrin/ sumo特异性蛋白酶1)与肿瘤缺氧微环境、肿瘤发生和转移有关。目的:探讨其在黑色素瘤耐药中的作用。材料和方法:先用浓度为2 μg/ml的达卡巴嗪(DTIC)处理A375和M14细胞系24 h,然后将细胞转移到新鲜培养基中增殖至最大密度的80%。然后重复此治疗周期共10天,之后DTIC浓度加倍。A375和M14的耐药细胞系均在持续治疗8个月后建立。使用实时逆转录聚合酶链反应(RT-qPCR)每月监测SENP1的表达水平,与未治疗的情况相比,1.5倍以上的变化被认为是显著的。结果:最后,研究发现SENP1在耐药细胞中上调约2.2-1.7倍。此外,正常A375细胞中SENP1的过表达提高了细胞抗DTIC的活力。研究还发现,Yes-associated protein (YAP)可在细胞质中形成蛋白凝聚体,并通过senp1介导的deSUMOylation增强其表达。结论:本研究提示黑色素瘤中泛素特异性蛋白酶SENP1与耐药呈正相关。其上调可能导致YAP的deSUMOylation发生改变,激活Hippo信号通路,增加黑色素瘤对DTIC的抗性。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Sentrin/SUMO-specific protease 1 contributes to drug resistance in melanoma by mediating the deSUMOylation of Yes-associated protein.

Sentrin/SUMO-specific protease 1 contributes to drug resistance in melanoma by mediating the deSUMOylation of Yes-associated protein.

Sentrin/SUMO-specific protease 1 contributes to drug resistance in melanoma by mediating the deSUMOylation of Yes-associated protein.

Sentrin/SUMO-specific protease 1 contributes to drug resistance in melanoma by mediating the deSUMOylation of Yes-associated protein.

Introduction: The effectiveness of chemotherapy in treating melanoma is limited due to drug resistance. Previous studies have shown that SENP1 (Sentrin/SUMO-specific protease 1) is related to the tumour hypoxic microenvironment, tumorigenesis and metastasis.

Aim: This study aimed to investigate its roles in drug resistance of melanoma.

Material and methods: Originally, a concentration of 2 μg/ml dacarbazine (DTIC) was employed in the treatment of A375 and M14 cell lines for a duration of 24 h. Subsequently, the cells were transferred to fresh medium and allowed to proliferate until reaching 80% of their maximum density. This treatment cycle was then repeated for a total of 10 days, following which the DTIC concentration was doubled. The establishment of drug-resistant cell lines for both A375 and M14 occurred after 8 months of sustained and continuous treatment. The expression level of SENP1 was monitored monthly using real-time reverse transcriptase-polymerase chain reaction (RT-qPCR), with a fold change above 1.5 compared to the untreated condition considered as significant.

Results: Finally, the study found that SENP1 was up-regulated by about 2.2-1.7 times in the drug-resistant cells. In addition, overexpression of SENP1 in normal A375 cells improved cell viability against DTIC. The study also found that Yes-associated protein (YAP) could form protein condensates in the cytoplasm while its expression was enhanced by SENP1-mediated deSUMOylation.

Conclusions: This study suggests that there is a positive correlation between the ubiquitin-specific protease SENP1 and drug resistance in melanoma. Its up-regulation may lead to changes in the deSUMOylation of YAP, activate the Hippo signalling pathway, and increase the resistance of melanoma to DTIC.

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
CiteScore
2.60
自引率
7.10%
发文量
107
审稿时长
6-12 weeks
期刊介绍: Advances in Dermatology and Allergology/Postępy Dermatologii i Alergologii is a bimonthly aimed at allergologists and dermatologists.
×
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