Silencing ubiquitin-conjugating enzyme 2C inhibits proliferation and epithelial-mesenchymal transition in pancreatic ductal adenocarcinoma.

Abstract

Ubiquitin-conjugating enzyme 2C (UBE2C) is a core ubiquitin-conjugating enzyme in the ubiquitin-proteasome system that promotes cell cycle progression. Previous studies have indicated that UBE2C mediates tumorigenesis and progression in various cancers, but its role in pancreatic ductal adenocarcinoma (PDAC) remains unclear. This study elucidated the function of UBE2C in PDAC tumorigenesis and progression by determining UBE2C expression via real-time qPCR, western blotting and immunohistochemistry. The associations between UBE2C expression and clinicopathological characteristics and survival were assessed using a tissue microarray based on a multicentre PDAC cohort. We found that UBE2C was strongly expressed in PDAC patient tissues and was negatively associated with clinical stage, lymph node metastasis, perineural invasion and survival (all P<0.05). Multivariate analysis revealed that high UBE2C expression is an independent risk factor for PDAC (P=0.001). In the PDAC cell lines CFPAC-1 and Panc-1, silencing UBE2C suppressed cell proliferation by inducing G1/S arrest mediated by downregulation of cyclin D1. Furthermore, UBE2C knockdown decreased the migration of PDAC cells invitro by downregulating epithelial-mesenchymal transition (EMT). RNA-seq analysis showed that upon silencing UBE2C in CFPAC-1 cells, cyclin D1 and vimentin were downregulated by approximately 3.5-fold and 2.6-fold, respectively, and the major enriched pathways were related to cell cycle progression. Experiments on tumour-bearing mice injected with CFPAC-1 cells indicated that UBE2C depletion significantly inhibits tumour growth invivo. These results suggest that UBE2C is involved in the development and progression of PDAC by regulating cell proliferation and EMT. UBE2C is a novel potential therapeutic target for pancreatic cancer. DATABASE: Data are available in the GEO database under accession number GSE137172.