TY - JOUR
T1 - UPF1 impacts on mTOR signaling pathway and autophagy in endometrioid endometrial carcinoma
AU - Zhang, Minfen
AU - Chen, Hui
AU - Qin, Ping
AU - Cai, Tonghui
AU - Li, Lingjun
AU - Chen, Ruichao
AU - Liu, Shaoyan
AU - Chen, Hui
AU - Lin, Wanrun
AU - Chen, Hao
AU - Strickland, Amanda L.
AU - Xiong, Hanzhen
AU - Jiang, Qingping
N1 - Funding Information:
The study was supported by Lin He’s Academician Workstation of New Medicine and Clinical Translation, Guangzhou Science and Technology Project (No. 202102010136) and Guangdong Natural Science Foundation (No. 2019A1515012194). The funds had no role in study design, data collection and analysis, the decision to publish, or the preparation of the manuscript.
Publisher Copyright:
© 2021 Zhang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited
PY - 2021/9/15
Y1 - 2021/9/15
N2 - 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.
AB - 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.
KW - UPF1
KW - autophagy
KW - endometrioid endometrial carcinoma
KW - mTOR
UR - http://www.scopus.com/inward/record.url?scp=85115641799&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85115641799&partnerID=8YFLogxK
U2 - 10.18632/aging.203421
DO - 10.18632/aging.203421
M3 - Article
C2 - 34520393
AN - SCOPUS:85115641799
SN - 1945-4589
VL - 13
SP - 21202
EP - 21215
JO - Aging
JF - Aging
IS - 17
ER -