PVT1/miR-136/Sox2/UPF1 axis regulates the malignant phenotypes of endometrial cancer stem cells

Abstract:Background: Tumor stem cells (TSCs) are thought to contribute to the progression and maintenance of cancer. Previous studies have suggested that plasmacytoma variant translocation 1 (PVT1) has a tumor-promoting effect on endometrial cancer; however, its mechanism of action in endometrial cancer stem cells (ECSCs) is unknown. The purpose of this study was to explore the mechanism by which PVT1 regulates the malignant behavior and stemness of ECSCs.Methods: The expression of PVT1, microRNA-136 (miR-136), Y chromosome (SRY)-related high-mobility-group box 2 (Sox2), and Up-frameshift protein 1 (UPF1) in endometrial cancer tissues and ECSCs were detected by quantitative real-time PCR (qRT-PCR) and western blot analysis. The binding sites were predicted and confirmed by bioinformatics analysis, dual-luciferase analysis, chromatin immunoprecipitation (ChIP) assays, and qRT-PCR. Through in vitro and in vivo experiments, the regulatory role of the PVT1/miR-136/Sox2/UPF1 axis in endometrial cancer was investigated.Results: PVT1 and Sox2 were highly expressed in endometrial cancer and ECSCs. They correlated with poor patient prognosis, promoting malignant behavior, and the stemness of endometrial cancer cells (ECCs) and ECSCs. In contrast, miR-136, which is underexpressed in endometrial cancer, had the opposite effect. PVT1 competed with Sox2 to bind miR-136 and regulate the expression of UPF1, thereby exerting a tumor-promoting effect on endometrial cancer.Conclusion: The PVT1/miR-136/Sox2/UPF1 axis plays an important role in the progression and maintenance of endometrial cancer. The results suggest a novel target for endometrial cancer therapies.