These authors contributed equally to this work Background: Pancreatic cancer (PC) is a highly lethal malignancy worldwide. Our previous study indicated that overexpression of USP34 could promote tumor growth in PC cells. Therefore, this study aimed to further investigate the role of USP34 during the tumorigenesis of PC. Methods: The level of USP34 in PANC-1 and MiaPaCa-2 cells transfected with USP34-shRNAs was detected by RT-qPCR. Moreover, transwell migration and Annexin V/PI analysis were conducted to detect cell migration and apoptosis, respectively. Results: In this study, downregulation of USP34 markedly inhibited proliferation and migration, and induced apoptosis in PANC-1 cells. Moreover, silencing of USP34 obviously downregulated the levels of PRR11 and p-p38 in PANC-1 cells. An in vivo study in nude mice bearing PANC-1 cell xenografts confirmed these results. Conclusion: Downregulation of USP34 could inhibit proliferation and migration in PANC-1 cells via inhibiting PRR11, and inactivating p38 MAPK signaling. Therefore, USP34 might be a potential therapeutic target for the treatment of PC.

Pancreatic cancer is known to be a fatal disease, which is difficult to be diagnosed in its early stages. Ubiquitin-Specific Protease 34 (USP34) are closely related to human cancers in the development and progression. However, there are rarely studies about the role of USP34 in pancreatic cancer. Thus, we aimed to investigate the effect of USP34 in human pancreatic cancer. Short-hairpin RNA targeting USP34 (USP34-shRNA) and USP34 overexpression lentivirus were used in the current study. The level of USP34 in human pancreatic cancer (PANC-1) cells were then analyzed by quantitative (q)RT-PCR. In addition, Western blotting was used to examine phosphorylated (p)-AKT, p-protein kinase C (PKC) and p-extracellular signal-regulated kinase (ERK) protein levels. CCK-8 assay, flow cytometry, and migration assay were used to detect cell proliferation, apoptosis and migration, respectively in vitro. According to the result of qRT-PCR and Western blotting, USP34-shRNA1 significantly downregulated USP34 gene level in PANC-1 cell. Subsequently, Western blotting assay indicated that USP34 silencing significantly down-regulated the expression of p-AKT and p-PKC in cells. On the other hand, USP34 overexpressing remarkably up-regulated the expression of p-AKT and p-PKC in cells. In addition, USP34 overexpression promoted PANC-1 cell proliferation and migration via up-regulating the proteins of p-AKT and p-PKC. Moreover, USP34 overexpression reversed AKT inhibitor and PKC inhibitor induced PACN-1 cell apoptosis. Our results indicated USP34 regulated h PANC-1 cell survival via AKT and PKC pathways, and which played a pro-survival role in human pancreatic cancer. Therefore, we suggested USP34 could be a potential therapeutic target for pancreatic cancer.