Department of Gastroenterology, Taicang Affiliated Hospital of Soochow University, The First People's Hospital of Taicang, Taicang, 215400, Jiangsu Province, China.
J Mol Histol. 2021 Apr;52(2):187-196. doi: 10.1007/s10735-020-09934-0. Epub 2021 Jan 4.
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）在多种恶性肿瘤中表达异常，提示 USP14 在肿瘤发生中具有重要作用。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，USP14 在 PDAC 组织中显著上调。值得注意的是，Kaplan-Meier 曲线表明，与 USP14 低表达的 PDAC 患者相比，USP14 高表达预示着预后显著更差。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。通过 MTT 分析、集落形成分析、流式细胞术分析以及细胞侵袭和迁移分析，我们发现敲低 USP14 可减弱 PDAC 细胞的增殖，诱导凋亡并抑制侵袭和迁移。过表达 USP14 可以增强增殖，阻止凋亡并促进 PDAC 细胞的侵袭和迁移。此外，USP14 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 的肿瘤发生中发挥重要作用，因此可能成为预防 PDAC 进展的有前途的治疗靶标。
