Abstract
Synaptophysin-like 1 (SYPL1) is a neuroendocrine-related protein. The role of SYPL1 in pancreatic ductal adenocarcinoma (PDAC) and the underlying molecular mechanism remain unclarified. Here, after analyzing five datasets (GSE15471, GSE16515, GSE28735, TCGA, and PACA-AU) and 78 PDAC patients from Sun Yat-sen University Cancer Center, we demonstrated that SYPL1 was upregulated in PDAC and that a high level of SYPL1 indicated poor prognosis. Bioinformatics analysis implied that SYPL1 was related to cell proliferation and cell death. To validate these findings, gain-of-function and loss-of-function experiments were carried out, and we found that SYPL1 promoted cell proliferation in vitro and in vivo and that it protected cells from apoptosis. Mechanistic studies revealed that sustained extracellular-regulated protein kinase (ERK) activation was responsible for the cell death resulting from knockdown of SYPL1. In addition, bioinformatics analysis showed that the expression of SYPL1 positively correlated with antioxidant activity. Reactive oxygen species (ROS) were upregulated in cells with SYPL1 knockdown and vice versa. Upregulated ROS led to ERK activation and cell death. These results suggest that SYPL1 plays a vital role in PDAC and promotes cancer cell survival by suppressing ROS-induced ERK activation.
Highlights
Pancreatic ductal adenocarcinoma (PDAC) is a lethal disease with a dismal 5-years survival rate of
Synaptophysin-like 1 (SYPL1) was elevated in pancreatic ductal adenocarcinoma (PDAC) cell lines compared to its expression in the HPDE6-C7 pancreatic duct epithelial cell line based on Western Blot (WB) and qPCR assays (Figures 1D,E)
The present study demonstrates that SYPL1, which is upregulated in tumor tissue and PDAC cell lines at the transcriptional level and protein level, is an independent factor associated with poor prognosis
Summary
Pancreatic ductal adenocarcinoma (PDAC) is a lethal disease with a dismal 5-years survival rate of
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have