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

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机构： [1]Department of Dermatology, Institute of Dermatology and Venereology, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, China. [2]Department of Paediatric Surgery, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, China.

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关键词： melanoma drug resistance SENP1 YAP Hippo signalling pathway

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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.This study aimed to investigate its roles in drug resistance of melanoma.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.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.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.Copyright: © 2025 Termedia Sp. z o. o.

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出版当年[2025]版：

大类 | 4 区医学

小类 | 4 区过敏 4 区皮肤病学

最新[2025]版：

大类 | 4 区医学

小类 | 4 区过敏 4 区皮肤病学

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出版当年[2024]版：

Q3 ALLERGY Q3 DERMATOLOGY

最新[2024]版：

Q3 ALLERGY Q3 DERMATOLOGY

影响因子： 1.7 最新[2024版] 1.9 最新五年平均 1.7 出版当年[2024版] 0 出版当年五年平均 1.7 出版前一年[2024版]

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第一作者机构： [1]Department of Dermatology, Institute of Dermatology and Venereology, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, China.

通讯作者：

通讯机构： [1]Department of Dermatology, Institute of Dermatology and Venereology, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, China. [*1]Department of Dermatology, Institute of Dermatology and Venereology, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, No. 32, Western 2nd Section, 1st Ring Rd, Qingyang District, Chengdu, Sichuan, 610072, China

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