Ubiquitin-specific peptidase 10, a deubiquitinating enzyme: Assessing its role in tumor prognosis and immune response

Abstract

Ubiquitin-specific peptidase 10 (USP10) is a member of the ubiquitin-specific protease family that removes the ubiquitin chain from ubiquitin-conjugated protein substrates. We performed a literature search to evaluate the structure and biological activity of USP10, summarize its role in tumorigenesis and tumor progression, and discuss how USP10 may act as a tumor suppressor or a tumor-promoting gene depending on its mechanism of action. Subsequently, we elaborated further on these results through bioinformatics analysis. We demonstrated that abnormal expression of USP10 is related to tumorigenesis in various types of cancer, including liver, lung, ovarian, breast, prostate, and gastric cancers and acute myeloid leukemia. Meanwhile, in certain cancers, increased USP10 expression is associated with tumor suppression. USP10 was downregulated in kidney renal clear cell carcinoma (KIRC) and associated with reduced overall survival in patients with KIRC. In contrast, USP10 upregulation was associated with poor prognosis in head and neck squamous cell carcinoma (HNSC). In addition, we elucidated the novel role of USP10 in the regulation of tumor immunity in KIRC and HNSC through bioinformatics analysis. We identified several signaling pathways to be significantly associated with USP10 expression, such as ferroptosis, PI3K/AKT/mTOR, TGF-β, and G2/M checkpoint. In summary, this review outlines the role of USP10 in various forms of cancer, discusses the relevance of USP10 inhibitors in anti-tumor therapies, and highlights the potential function of USP10 in regulating the immune responses of tumors.

Keywords: USP10 inhibitors; deubiquitination; epigenetic modification; immune response; tumorigenesis.

Figure 1

The structure of USP10. Human USP10 contains an Ataxin 2C domain and a USP domain. The Ataxin2C domain is approximately 250 residues long, and is located at the C-terminus of eukaryotic ataxin-2. The USP domain consists of a catalytic site, protein-protein interaction sites, and localization domains. USP10, Ubiquitin-specific peptidase 10.

Figure 2

The gene and protein expressions of USP10 in pan-cancers based on TCGA and CPTAC databases. (A) The gene expressions of USP10 in pan-cancers based on TCGA database; (B) The protein expressions of USP10 in pan-cancers based on CPTAC database. Red color: tumor tissues; Blue color: normal tissues. USP10, Ubiquitin-specific peptidase 10; TCGA, The Cancer Genome Atlas; CPTAC, Clinical Proteomic Tumor Analysis Consortium. *P < 0.05; **P < 0.01; ***P < 0.001.

Figure 3

Analysis of the TISIDB and Kaplan-Meier plotter website indicated the role of USP10 in tumors and immune subtype. (A) HNSC patients with increased USP10 expression had lowered OS, however, high levels of USP10 were associated with prolonged OS in KIRC patients. (B) The correlation between USP10 expression and tumor stage in KIRC patients. (C) USP10 was correlated with the immune subtype in KIRC. NS, not significant. USP10, Ubiquitin-specific peptidase 10; HNSC, head and neck squamous cell carcinoma; OS, overall survival; KIRC, kidney renal clear cell carcinoma.

Figure 4

USP10 was positively correlated with immunosuppressive molecules (A), immunostimulatory molecules (B), chemokines (C), MHC molecules (D), lymphocytes (E), and MHC receptors (F). USP10, Ubiquitin-specific peptidase 10; MHC, major histocompatibility complex.

Figure 5

USP10 was positively correlated with TAP2 and TGFBR1 in HNSC.

Figure 6

USP10 was positively correlated with CD274 (A), B2M (B), CXCL16 (C), myeloid dendritic cell (E), and CCR1 (F), but negatively correlated with TNFRSF25 (D) in KIRC. USP10, Ubiquitin-specific peptidase 10; TAP2, transporter associated with antigen processing 2; TGFBR1, transforming growth factor beta receptor 1; HNSC, head and neck squamous cell carcinoma; B2M, β2-microglobulin; CXCL16, C-X-C motif ligand 16; CCR1, CC Chemokine receptor 1; TNFRSF25, TNF receptor superfamily 25; KIRC, kidney renal clear cell carcinoma.

Figure 7

The signaling pathways significantly related to USP10 in HNSC included EMT, ECM, angiogenesis, apoptosis, tumor inflammation, G2/M checkpoint, ferroptosis, PI3K/AKT/mTOR, MYC, TGF-β, tumor proliferation, reaction oxygen species, DNA replication, and collagen formation. USP10, Ubiquitin-specific peptidase 10; HNSC, head and neck squamous cell carcinoma; EMT, Epithelial-mesenchymal transition; ECM, extracellular matrix.

Figure 8

The signaling pathways significantly related to USP10 in KIRC included ferroptosis, DNA repair, G2/M checkpoint, inflammatory response, PI3K/AKT/mTOR, p53, c-Myc, TGF-β, and ROS. USP10, Ubiquitin-specific peptidase 10; KIRC, kidney renal clear cell carcinoma; ROS, reactive oxygen species.