Upregulation of deubiquitinase PSMD14 in lung adenocarcinoma (LUAD) and its prognostic significance
Upregulation of deubiquitinase PSMD14 in lung adenocarcinoma (LUAD) and its prognostic significance
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肺腺癌（LUAD）中去泛素酶 PSMD14 的上调及其预后意义
DOI：
10.7150/jca.39539
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发表时间：
2020-01-01
影响因子：
3.9
通讯作者：
Li, Dawei
中科院分区：
文献类型：
--
作者：
Zhang, Ling;Xu, Hui;Li, Dawei
PSMD 14是一种19 S-蛋白酶体相关的去泛素化酶，可促进20 S蛋白酶体核心颗粒对蛋白质的降解。尽管越来越多的证据表明PSMD 14通过促进肿瘤生长而成为一种关键的致癌因子，但PSMD 14在非小细胞肺癌（NSCLC）中的表达和功能仍不清楚。在这项研究中，我们评估了PSMD 14的表达，并将其与NSCLC的临床病理特征和患者生存率相关联。我们还确定了PSMD 14在调节肺腺癌（LUAD）细胞生长中的作用。结果显示，与邻近的非癌组织相比，PSMD 14在人NSCLC组织中的表达显著上调。在LUAD患者中，PSMD 14水平与肿瘤大小、淋巴结浸润和TNM分期相关。重要的是，高PSMD 14表达与LUAD患者的总生存期（OS）和无病生存期（DFS）相关。此外，敲低PSMD 14显著抑制细胞生长，并通过增加LUAD细胞中p21的稳定性引起G1期阻滞和细胞衰老。PSMD 14敲除还通过增加H1299细胞中切割的caspase-3水平促进细胞凋亡。PSMD 14可能作为LUAD患者的潜在预后标志物和治疗靶点。
PSMD14 is a 19S-proteasome-associated deubiquitinating enzyme that facilitates protein degradation by the 20S proteasome core particle. Although accumulating evidence indicates that PSMD14 has emerged as a critical oncogenic factor by promoting tumor growth, the expression and function of PSMD14 in non-small cell lung cancer (NSCLC) remain largely unknown. In this study, we assessed PSMD14 expression and correlated it with clinical-pathological features and patient survival in NSCLC. We also determined the roles of PSMD14 in the regulation of lung adenocarcinoma (LUAD) cell growth. The results showed that PSMD14 expression was significantly upregulated in human NSCLC tissues compared with adjacent non-cancerous tissues. The PSMD14 level was associated with tumor size, lymph node invasion, and TNM stage in LUAD patients. Importantly, high PSMD14 expression was associated with poor overall survival (OS) and disease-free survival (DFS) in LUAD patients. Further, knockdown of PSMD14 significantly inhibited cell growth and caused G1 arrest and cellular senescence by increasing p21 stability in LUAD cells. PSMD14 knockdown also promoted cell apoptosis by increasing cleaved caspase-3 levels in H1299 cells. PSMD14 may serve as a potential prognostic marker and therapeutic target for LUAD patients.