COP9 signalosome 8 mediated autophagy drives proliferation, invasion, and metastasis in pancreatic ductal adenocarcinoma.

The present study aimed to explore the role of COP9 signalosome 8 (COPS8) as a novel molecule in pancreatic ductal adenocarcinoma (PDAC). A total of 9 genes were first identified by intersecting the differential genes of the GSE15471 and GSE62165 datasets with 248 Neddylation genes from the Reactome Pathway Database. The association between disease-free survival and the 9 genes in patients with PDAC was analyzed. Analysis using The Cancer Genome Atlas, Gene Expression Omnibus and Gene Expression Profiling Interactive Analysis databases revealed that COPS8 was highly expressed in patients with PDAC, and PDAC tissues exhibited significantly higher COPS8 expression levels compared to those found in paracancerous tissues. Finally, the above results were verified by cellular experiments, reverse transcription-quantitative PCR, Western blotting and immunohistochemistry. The mRNA expression levels of COPS8 were significantly elevated in the pancreatic cancer cell lines PANC-1and MIA PaCa-2 compared to those in HPNE normal pancreatic cells, and the protein expression levels of COPS8 were also significantly elevated in the pancreatic cancer cells PANC-1 and MIA PaCa-2. COPS8 protein was significantly increased in cancer tissues of patients with pancreatic cancer compared to paracancerous tissues. The proliferative, migratory and invasive abilities of PANC-1 and MIA PaCa-2 cells were significantly reduced after knockdown of COPS8. The results showed that knockdown of COPS8 in PANC-1 and MIA PaCa-2 cells decreased Microtubule-associated proteins 1A/1B light chain 3B (LC3Ⅱ/LC3Ⅰ), while Sequestosome 1 (P62/SQSTM1) expression was elevated. COPS8 may promote the proliferation, invasion, and metastasis of pancreatic cancer cells by regulating autophagy.