Expression of Ubiquitin-specific protease 7 in oral squamous cell carcinoma promotes tumor cell proliferation and invasion.

Xiaojie Yang,Guangying Qi,Lihua Zhou,Jinfeng Yang,Sisi Mi,Jiamin Jin

doi:10.1590/1678-4685-gmb-2021-0058

Abstract

Oral Squamous Cell Carcinoma (OSCC) is the most common malignant cancer affecting oral cavity. Recent studies have demonstrated that Ubiquitin-specific protease 7 (USP7) was upregulated in several types of cancers. USP7 expression was associated with various proto-oncogenes and tumor suppressor genes. However, USP7 expression level and its functional role in OSCC is unclear. In the current study, we showed that USP7 expression in OSCC tissues was generally upregulated compared to normal adjacent tissues by using IHC. Furthermore, statistical analysis uncovered that USP7 expression was positively correlated with Ki-67, MMP2, VEGF in OSCC tissues. Importantly, high USP7 expression was significantly correlated with lymph node metastasis and histological differentiation in OSCC patients. So, our hypothesis is that USP7 plays a tumor-promoting role in OSCC. Knocking down of USP7 in tumor cells not only suppressed HSC3 cells proliferation, migration and invasion, but also promoted cell apoptosis. Moreover, USP7 siRNA blocked the activation of Akt/ERK signaling pathway. In conclusion, data presented here suggests that USP7 promotes the progression of OSCC. USP7 may be used as a new therapeutic target for OSCC diagnosis and treatment.

Highlights

Oral cancer is a type of severe malignant head and neck tumor, with about 90% oral cancer cases are Oral Squamous Cell Carcinoma (OSCC) (Bray et al, 2018)
Ubiquitin-specific protease 7 (USP7) and Ki-67 were primarily localized in the nuclei, while matrix metalloproteinase 2 (MMP2) and Vascular endothelial growth factor (VEGF) were localized in the cytoplasm
These findings demonstrated that USP7 expression was elevated in OSCC tissues, suggesting that USP7 and its relative genes Ki-67, MMP2 and VEGF may promote the development of OCSS

Summary

Introduction

Oral cancer is a type of severe malignant head and neck tumor, with about 90% oral cancer cases are Oral Squamous Cell Carcinoma (OSCC) (Bray et al, 2018). The 5-year survival rate is about 39% (Zhang et al, 2019). The ubiquitin proteasome system is important for maintaining protein turnover for cancer progression (Young et al, 2019). We have previously demonstrated that USP22 was upregulated in OSCC and hepatocellular carcinoma (Tang et al, 2015; Liu et al, 2019). USP22 can regulate the expression of cell cycle related proteins in order to promote cancer cell growth (Liu et al, 2019). Recent studies show that USP7, which is involved in tumor-genesis and process (Song et al, 2008; Zhang et al, 2016), could be used for novel drug target in cancer therapy (Zhou et al, 2018). USP7 expression is closely related to tumor

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