Previous studies have shown aberrant expression of ubiquitin-specific protease 14 (USP14) in multiple malignancies, suggesting an important role of USP14 in tumorigenesis. However, the functional role of USP14 in pancreatic ductal adenocarcinoma (PDAC) has never been elucidated. In this study, we found that USP14 was remarkably upregulated in PDAC tissues compared with normal pancreatic tissues. Notably, Kaplan–Meier curves showed that high expression of USP14 predicted significantly worse prognosis in PDAC patients than low expression of USP14. To determine whether USP14 could regulate the proliferation, apoptosis and metastasis of PDAC cells, we knocked down endogenous USP14 or overexpressed exogenous USP14 in Panc-1 and BxPC-3 cells. Using MTT assays, colony formation analyses, flow cytometry assays, and cell invasion and migration assays, we found that knockdown of USP14 attenuated proliferation, induced apoptosis and restrained invasion and migration of PDAC cells. Overexpression of USP14 could enhance proliferation, prevent apoptosis and promote invasion and migration of PDAC cells. In addition, USP14 could regulate the expression of cyclin D1, PCNA and E-cadherin, three important carcinogenic factors, in PDAC cells. These findings suggest that USP14 might play an important role in promoting the tumorigenesis of PDAC and thus be a promising therapeutic target to prevent PDAC progression.

先前的研究表明，泛素特异性蛋白酶 14 (USP14) 在多种恶性肿瘤中存在异常表达，表明 USP14 在肿瘤发生中发挥重要作用。然而，USP14 在胰腺导管腺癌 (PDAC) 中的功能作用尚未阐明。在这项研究中，我们发现与正常胰腺组织相比，PDAC 组织中 USP14 的表达显着上调。值得注意的是，Kaplan-Meier 曲线显示，与 USP14 低表达相比，USP14 高表达预示 PDAC 患者预后显着较差。为了确定USP14是否可以调节PDAC细胞的增殖、凋亡和转移，我们在Panc-1和BxPC-3细胞中敲低内源性USP14或过表达外源性USP14。使用MTT测定、集落形成分析、流式细胞术测定以及细胞侵袭和迁移测定，我们发现USP14的敲低可减弱PDAC细胞的增殖、诱导细胞凋亡并抑制侵袭和迁移。 USP14的过表达可以增强PDAC细胞的增殖、防止细胞凋亡并促进侵袭和迁移。此外，USP14还可以调节PDAC细胞中三个重要致癌因子cyclin D1、PCNA和E-cadherin的表达。这些发现表明USP14可能在促进PDAC肿瘤发生中发挥重要作用，因此成为预防PDAC进展的有前景的治疗靶点。