{"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。
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.