Abstract
SENP3, a sentrin/SUMO2/3-specific protease, is recognized as a transcriptional factor that accumulates under cellular oxidative stress and plays a significant role in the removal of SUMO2/3 modification. In our study, we examined a TCGA dataset and found that the transcripts per million (TPM) value of SENP3 is high in sarcoma, including osteosarcoma (OS). We found that SENP3 was highly expressed in OS cancer tissues when compared with osteofibrous dysplasia tissues. The survival data of SENP3 in TCGA showed that the sarcoma patients with higher SENP3 expression levels showed poor prognosis. In vitro, SENP3 knockdown in OS cancer cells inhibited cell proliferation, migration, and invasion and induced apoptosis. In contrast, SENP3 overexpression reversed these effects. Next, we found that SENP3 inhibited the expression of E-cadherin (E-Cad) by increasing methylation of the E-Cad promoter. Finally, E-Cad expression was increased in the OS cell line MG63 following methylation, and the cell proliferation, migration, and invasion capacity were decreased. In summary, SENP3 played a significant role in OS carcinogenesis and may act as a potential biomarker in the diagnosis and treatment of OS.