Clinical Significance of Ubiquitin Specific Protease 7 (USP7) in Predicting Prognosis of Hepatocellular Carcinoma and its Functional Mechanisms

Abstract

BackgroundsHepatocellular carcinoma (HCC) accounts for one of the most prevalent cancer types in the world. The ubiquitin specific protease 7 (USP7), a kind of deubiquitylating enzyme, has been reported to play multifaceted roles in different tumor types. The aim of this study was to investigate the expression and function of USP7 in HCC.Material/MethodsImmunohistochemical staining and quantitative PCR were performed to explore the expression of USP7 in both HCC tissues and adjacent normal liver tissues. Chi-square test, univariate analysis, and multivariate analysis were conducted to statistically evaluate the clinical significance of USP7 in HCC. Proliferation, migration, and invasion capacities of HCC cells were assessed after overexpressing or silencing USP7.ResultsBoth the RNA and protein levels of USP7 were upregulated in HCC tissues compared to normal liver tissues. High expression of USP7 was correlated with advanced tumor stage and poor overall survival. Moreover, USP7 was identified as a novel independent prognostic factor for HCC patients. Cellular studies showed that USP7 could enhance the proliferation, migration, and invasion capacities of HCC cells, thereby promoting tumor progression.ConclusionsHigh expression of USP7 is frequent in HCC tissues, which promotes tumor proliferation and invasion, and is correlated with a poor overall survival. Targeting USP7 may be a novel direction for the drug development of HCC therapy.

Targeting the overexpressed USP7 inhibits esophageal squamous cell carcinoma cell growth by inducing NOXA‐mediated apoptosis

“…11,12 Deubiquitinase USP7, also known as HAUSP was first reported by Everett et al 13 as a novel member of the ubiquitin-specific protease family to interact with Herpes simplex virus type one immediate-early protein Vmw110 and to participate in the early stages of viral infection. Recent reports showed that USP7/HAUSP regulated many substrates and was closed to tumor progression, [14][15][16][17][18][19][20][21] DNA damage, 22,23 epigenetic regulation, [24][25][26] and immune response. 27 Overexpression of USP7/HAUSP was associated with several tumors' poor prognosis, [14][15][16][17] tumor differentiation, 18 or migration and invasion.…”

“…Recent reports showed that USP7/HAUSP regulated many substrates and was closed to tumor progression, [14][15][16][17][18][19][20][21] DNA damage, 22,23 epigenetic regulation, [24][25][26] and immune response. 27 Overexpression of USP7/HAUSP was associated with several tumors' poor prognosis, [14][15][16][17] tumor differentiation, 18 or migration and invasion. 14,15,19 On the other hand, USP7/HAUSP might act as tumor suppressor in NSCLCs through p53-dependent pathways.…”

Increase in the nuclear localization of PTEN by the Toxoplasma GRA16 protein and subsequent induction of p53‐dependent apoptosis and anticancer effect

“…1,[4][5][6] Thus, HAUSP plays a crucial role in cell proliferation and differentiation by deubiquitinating MDM2 and PTEN; HAUSP suppression is vital for anticancer therapeutic intervention, simultaneously focusing on HAUSP as a candidate druggable target. [1][2][3][6][7][8] Conversely, the negative regulation of HAUSP exhibits a crucial clinical significance for estimating the prognosis of tumour suppression. [1][2][3][6][7][8] Conversely, the negative regulation of HAUSP exhibits a crucial clinical significance for estimating the prognosis of tumour suppression.…”

“…[1][2][3][4][5][6] Herpes virus-associated ubiquitin-specific protease is overexpressed in various human cancer types, including prostate cancer, multiple myeloma tumours, neuroblastoma, epithelial ovarian cancer, non-small cell lung cancer, breast cancer, hepatocellular carcinoma (HCC) and lymphocytic leukaemia. [1][2][3][6][7][8] Conversely, the negative regulation of HAUSP exhibits a crucial clinical significance for estimating the prognosis of tumour suppression. 5,7 Thus, identification of HAUSP inhibitors is imperative for the therapeutic intervention of cancer.…”

“…This finding could be construed as debatable owing to the existence of conflicting results for Hep3B cells, for example, HAUSP-knockdown using siRNA inhibited cell proliferation in Hep3B, and HAUSP inhibition using p5091 also induced apoptosis and cell growth arrest in p53-mutated lymphocytic leukaemia cell line MEC-1 7,8. This finding could be construed as debatable owing to the existence of conflicting results for Hep3B cells, for example, HAUSP-knockdown using siRNA inhibited cell proliferation in Hep3B, and HAUSP inhibition using p5091 also induced apoptosis and cell growth arrest in p53-mutated lymphocytic leukaemia cell line MEC-1 7,8.…”