Abstract
Most EEC cases are associated with activities of the mTOR pathway, which regulates protein synthesis, cell growth and autophagy. While Up-Frameshift 1(UPF1) is a key protein factor in the nonsense-mediated mRNA degradation pathway (NMD), its role in carcinogenesis of EEC remains unclear. In this study, we first evaluated the expression level of UPF1 in EEC tissues and cell lines. Then, we investigated the effect of UPF1 on cellular function and mTOR signaling pathway; these effects were further validated in vivo. Finally, its effect on autophagy was evaluated by western blot and GFP-mRFP-LC3 staining. UPF1 expression in the EEC tissue samples was significantly higher than that of matched normal tissue samples. Overexpression of UPF1 promoted migration and invasion of EEC cells. Conversely, depletion of UPF1 suppressed migration and invasion of EEC cells. In addition, overexpression of UPF1 increased the in vivo growth of our EEC xenograft tumors. Finally, UPF1 increased the activity of the mTOR/P70S6K/4EBP1 signaling pathway and inhibited autophagy in EEC cells. These findings suggest that UPF1 functions as an oncogene to promote EEC carcinogenesis. Our findings propose UPF1 as a new potential therapeutic target for EEC.
Highlights
Endometrial cancer (EC) is one of the most common malignant tumors in gynecological system
Most endometrial carcinoma (EEC) are related with the Mammalian target of rapamycin (mTOR) pathway, which is responsible for regulating protein synthesis and cell growth [1,2,3]. mTORC1 and mTORC2 are the catalytic subunits of two biochemically distinct molecular complexes of mTOR
To evaluate Up-frameshift 1 (UPF1) expression in EEC, UPF1 mRNA levels from 42 paired fresh EEC tissue samples and corresponding adjacent normal endometrium were measured by real-time qPCR
Summary
Endometrial cancer (EC) is one of the most common malignant tumors in gynecological system. ECs often exhibit mixed features at the clinical, pathologic and molecular levels. Within this broad spectrum of malignancies, endometrioid endometrial carcinoma (EEC) is the most common histological type. Autophagy-related genes, such as BECLIN1, Atg, and Atg, are included in the complex mechanisms of regulating the progression of various cancers. It is widely accepted www.aging-us.com that LC3 is a marker of the autophagic membrane, and P62 is a commonly used marker for autophagy degradation [8,9,10,11]
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