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Review
. 2020 Jan;19(1):30-44.
doi: 10.3892/ol.2019.11062. Epub 2019 Nov 7.

The role of deubiquitinating enzymes in gastric cancer

Jiangang Sun  1 , Xiaojing Shi  2 , M A A Mamun  2 , Yongshun Gao  1
Affiliations
Review

The role of deubiquitinating enzymes in gastric cancer

Jiangang Sun et al. Oncol Lett. 2020 Jan.

Abstract

The epigenetic regulation of gene expression (via DNA methylation, histone modification and microRNA interference) contributes to a variety of diseases, particularly cancer. Protein deubiquitination serves a key role in the mechanism underlying histone modification, and consequently influences tumor development and progression. Improved characterization of the role of ubiquitinating enzymes has led to the identification of numerous deubiquitinating enzymes (DUBs) with various functions. Gastric cancer (GC) is a highly prevalent cancer type that exhibits a high mortality rate. Latest analysis about cancer patient revealed that GC is sixth deadliest cancer type, which frequently occur in male (7.2%) than female (4.1%). Complex associations between DUBs and GC progression have been revealed in multiple studies; however, the molecular mechanism underpinning the metastasis and recurrence of GC is yet to be elucidated. Generally, DUBs were upregulated in gastric cancer. The relation of DUBs and tumor size, classification and staging was observed in GC. Besides, 5-yar survival rate of patients with GC is effeccted by expression level of DUBs. Among the highly expressed DUBs, specifically six DUBs namely UCHs, USPs, OTUs, MJDs, JAMMs and MCPIPs effect on this survival rate. Consequently, the association between GC and DUBs has received increasing attention in recent years. Therefore, in the present review, literature investigating the association between DUBs and GC pathophysiology was analyzed and critically appraised.

Keywords: deubiquitinating enzymes; gastric cancer; survival.

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Figures

Figure 1.
Figure 1.
Members of the DUB family. The DUB family contains numerous members, which have been divided into subfamilies. The USPs are the largest subfamily of DUBs, and were further divided into 9 subfamilies (USP1-9) in the present study; CYLD lysine 63 deubiquitinase and USPL1 have been listed as other USP members. The first digits indicates the subfamily, for example, USP14 belongs to the USP1 subfamily. The subfamily classification of the ovarian tumor-related protease family refers to existing taxonomies (102). DUB, deubiquitinating enzyme; USP, ubiquitin-specific protease.
Figure 2.
Figure 2.
Gene expression profile of ubiquitin C-terminal hydrolases between gastric cancer samples and paired normal tissues. Data were extracted using the Gene Expression Profiling Interactive Analysis website. UCH, Ubiquitin C-terminal hydrolase; BAP1, BRCA1 associated protein-1.
Figure 3.
Figure 3.
Gene expression profiles of ubiquitin-specific proteases between gastric cancer samples and paired normal tissues. Data were extracted using the Gene Expression Profiling Interactive Analysis website. USP, ubiquitin-specific protease. CYLD, CYLD lysine 63 deubiquitinase.
Figure 4.
Figure 4.
Gene expression profiles of ovarian tumor-related proteases between gastric cancer samples and paired normal tissues. Data were extracted using the Gene Expression Profiling Interactive Analysis website. NF, not found.
Figure 5.
Figure 5.
Gene expression profiles of Machado-Joseph disease protein domain proteases between gastric cancer samples and paired normal tissues. Data were extracted using the Gene Expression Profiling Interactive Analysis website. NF, not found. ATXN, ataxin; JOSD, Josephin domain containing.
Figure 6.
Figure 6.
Gene expression profiled of the Jab1/MPN domain-associated metalloisopeptidases between gastric cancer samples and paired normal tissues. Data were extracted using the Gene Expression Profiling Interactive Analysis website. NF, not found.
Figure 7.
Figure 7.
Gene expression profiles of monocyte chemotactic protein-induced proteins between gastric cancer samples and paired normal tissues. Data were extracted using the Gene Expression Profiling Interactive Analysis website. NF, not found. MCPIP, monocyte chemotactic protein-induced proteins.
Figure 8.
Figure 8.
Expression of DUBs in GC. Data were extracted using the Gene Expression Profiling Interactive Analysis website. (A) T>N (n=71); T
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