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Gene & Protein in Disease Structure and function of USP7

6.4. USP7 in cancers Prostate cancer is a form of cancer that develops in

Among the diseases, cancers are the most intensively the prostate, and is considered a slow-growing tumor.
investigated research area in terms of USP7. USP7 is highly The incidence of prostate cancer is increasing by 2–3%
[156]
overexpressed in most tumors, such as breast cancer, every year, with more than 10% of death in male . As
medulloblastoma, T-cell leukemia, ovarian cancer, HCC, a histone methylase, EZH2 plays an important role in the
MM, prostate cancer, and CML [15-17,20,23,38,107] , suggesting development of diverse tumor, including prostate cancer.
the role of USP7 in tumor promotion. Relative protein Studies identified that the deubiquitinase USP7 is highly
expression in Figure 1 shows USP7 expression in several expressed in prostate cancer, and more importantly, USP7
cancers [155] . interacts with EZH2 and increases its protein stabilization
through its deubiquitinating activity. In contrast, a
USP7 is overexpressed in human breast cancer, and its reduction in USP7 expression fails to rescue the degradation
expression is positively correlated with its substrate protein, of EZH2 through the UPP, resulting in the inhibition of
PHF8. USP7 decreases the polyubiquitination of PHF8 cell growth and the suppression of tumor progression .
[23]
and increases the expression of cyclin A2 protein, which is Consistent with previous reports, USP7-specific inhibitors
an essential and important protein for the development of in combination with PARP inhibitor can produce a more
breast cancer . Estrogen receptor α (ERα) is reported to lethal effect on prostate cancer cells, suggesting USP7 as a
[15]
be overexpressed in about 70% breast tumors. Studies have promising therapeutic target for prostate cancer.
identified the positive correlation between ERα and USP7,
depending on the deubiquitinase activity of USP7 and HCC is one of the most common malignancies in
their interactions, where USP7 silencing led to cell growth China, and its incidence is ranked the third highest
inhibition and delayed tumor growth [106] . In addition, USP7 across the country [157] . Studies have identified that USP7
has also been proven to be associated with poor prognosis is frequently overexpressed in HCC tissues, and positively
of breast cancer, suggesting USP7 as a potential target for correlated with poor prognosis, indicating UPP’s role in
clinical treatment. Further, USP7 acts as a DUB of p53; the development of HCC [158] . In addition, recent studies
therefore, the negative effects of p53 protein degradation have demonstrated that USP7 promotes the proliferation,
should be considered when using USP7 inhibitors for invasion, and migration of HCC cells through activating
breast cancer treatment. the bcl-2-like protein 4 (Bax), which subsequently

A

B

Figure 1. USP7 is highly expressed in cancer. (A) USP7 expression analysis of TCGA samples from The Human Protein Atlas database. Image reproduced
from USP7 Protein Expression Summary; Malignant cells showed weak to moderate nuclear and cytoplasmic immunoreactivity (antibody CAB008108);
available from https://www.proteinatlas.org/ENSG00000187555-USP7/pathology (image credit: The Human Protein Atlas). (B) Immunohistochemical
staining of USP7 in representative tumors via the Human Protein Atlas (HPA) database. USP7 is highly expressed in a variety of tumors, including colorectal
cancer, breast cancer, prostate cancer, and lung cancer. Image reproduced from USP7 Protein Expression; available from https://www.proteinatlas.org/
ENSG00000187555-USP7/pathology (image credit: The Human Protein Atlas).

Volume 1 Issue 2 (2022) 7 https://doi.org/10.36922/gpd.v1i2.118