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.
Retinal microvascular endothelial cell (RMEC) injury plays an important role in the pathophysiology diabetic retinopathy (DR). The GTPase dynamin-related protein 1 (Drp1), crucial to mitochondrial dynamics , has been implicated in hyperglycaemia-induced microvascular damage. Moreover, Drp1 can be deSUMOylated by the enzyme sentrin/SUMO-specific protease 3 (SENP3). Whether SENP3/deSUMOylated Drp1 can aggravate DR is unclear. Therefore, we designed this experiment to investigate the role of SENP3/desumoylated Drp1 in DR in vitro and in vivo. Murine RMECs (mRMECs) were classified into a control (CON), high-glucose (HG) and high-glucose + SENP3-siRNA (HG-siRNA) groups. The SENP3 and SUMOylated/deSUMOylated drp1 levels, mitochondrial morphology, mitochondrial membrane potential (MMP) and apoptosis rate were evaluated. In vivo, mice were assigned to a normal, type 2 diabetic or type 2 diabetic SENP3-siRNA mouse groups. Then, blood–retinal barrier function and retinal tissue structure were evaluated. As compared to those in the control group, the SENP3 and Drp1 levels, degree of mitochondrial fragmentation, extent of MMP loss and apoptosis rate of mRMECs were significantly increased in the HG group. However, inhibited SENP3 expression increased the level of SUMOylated Drp1 in the mRMECs and reduced the hyperglycaemia-induced mitochondrial damage and apoptosis rate. These experimental results were confirmed by diabetic animal experiments showing that inhibited SENP3 expression attenuated the increase in retinal permeability and diabetic retinopathy, suggesting that SENP3/deSUMOylated Drp1 activation aggravated DR by disrupting mitochondrial dynamics and apoptosis. Furthermore, blocking SENP3 expression significantly attenuated RMEC damage and DR.
危险品化学品经营许可证（带存储）