USP34 Regulated Human Pancreatic Cancer Cell Survival <i>via</i> AKT and PKC Pathways

Abstract

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.

<p>Downregulation of USP34 Inhibits the Growth and Migration of Pancreatic Cancer Cells via Inhibiting the PRR11</p>

“…Our previous study indicated that USP34 could promote human PC cell survival via activating AKT and PKC pathways. 12 In this study, we found that downregulation of USP34 could inhibit the tumor growth in PANC-1 cells via inhibiting the PRR11 and inactivating p38 signaling in vitro and in vivo. To sum up, we demonstrated that USP34 plays an oncogenic role in PC.…”

“…22 In our previous study, we found that the expression of USP34 was markedly upregulated in PC tissues, compared with para-cancerous tissue samples. 12 Moreover, downregulation of USP34 could inhibit proliferation and migration, and induce apoptosis in PANC-1 cells. Meanwhile, downregulation of USP34 could inhibit the tumor growth of PANC-1 xenograft in vivo.…”

“…11 In the previous study, we found that USP34 played a pro-survival role in PC cells via activating AKT and PKC pathways. 12 However, the mechanisms by which USP34 regulated the apoptosis of PC cells needs further investigation.…”

Ubiquitin-Specific Protease 34 Inhibits Osteoclast Differentiation by Regulating NF-κB Signaling

“…In addition to NF‐κB signaling, USP34 was also found to regulate the stability of several proteins and signaling in other systems, including Wnt signaling, protein kinase B (PKB/Akt), protein kinase C (PKC), and ubiquitin ligase . Because these proteins and involved pathways also play a role in osteoclast function, future studies might help to clarify whether USP34 targets these proteins in the osteoclast lineage …”

The deubiquitinase USP34 stabilizes SOX2 and induces cell survival and drug resistance in laryngeal squamous cell carcinoma

“…9 Another paper also showed that overexpression of USP34 could promote pancreatic cancer cell proliferation and migration by increasing the expression of p-AKT and p-PKC. 10 Additionally, USP34 could stabilize axin protein, and promote β-cateninmediated transcription. 11 However, the function and mechanism of USP34 in LSCC are still unclear.…”