J Cancer 2020; 11(10):2962-2971. doi:10.7150/jca.39539

Research Paper

Upregulation of deubiquitinase PSMD14 in lung adenocarcinoma (LUAD) and its prognostic significance

Ling Zhang1, Hui Xu2, Chunping Ma2, Jieru Zhang3, Yuanjie Zhao4, Xiaomei Yang5, Shusheng Wang4✉, Dawei Li1✉

1. Center for Translational Medicine, The Affiliated Zhangjiagang Hospital of Soochow University, 68 Jiyang W Rd, Suzhou, 215600, China.
2. Department of Thoracic Surgery, The Affiliated Zhangjiagang Hospital of Soochow University, 68 Jiyang W Rd, Suzhou, 215600, China.
3. Department of Respiratory & Critical Care Medicine, The Affiliated Zhangjiagang Hospital of Soochow University, 68 Jiyang W Rd, Suzhou, 215600, China.
4. Department of General Surgery, The Affiliated Zhangjiagang Hospital of Soochow University, 68 Jiyang W Rd, Suzhou, 215600, China.
5. Department of Emergency, The Affiliated Zhangjiagang Hospital of Soochow University, 68 Jiyang W Rd, Suzhou, 215600, China.

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Citation:
Zhang L, Xu H, Ma C, Zhang J, Zhao Y, Yang X, Wang S, Li D. Upregulation of deubiquitinase PSMD14 in lung adenocarcinoma (LUAD) and its prognostic significance. J Cancer 2020; 11(10):2962-2971. doi:10.7150/jca.39539. Available from http://www.jcancer.org/v11p2962.htm

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Abstract

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.

Keywords: PMSD14, deubiquitinating enzyme, lung adenocarcinoma, prognosis, senescence, apoptosis