Ubiquitin specific peptidase 5 promotes ovarian cancer cell proliferation through deubiquitinating HDAC2

Abstract

Globally, epithelial ovarian cancer (EOC) is the most common gynecological malignancy with poor prognosis. The expression and oncogenic roles of ubiquitin specific peptidase 5 (USP5) have been reported in several cancers except EOC. In the current study, USP5 amplification was highly prevalent in patients with EOC and associated with higher mRNA expression of USP5. USP5 amplification and overexpression was positively correlated with poor prognosis of patients of ovarian serous carcinomas. Disruption of USP5 profoundly repressed cell proliferation by inducing cell cycle G0/G1 phase arrest in ovarian cancer cells. Additionally, USP5 knockdown inhibited xenograft growth in nude mice. Knockdown of USP5 decreased histone deacetylase 2 (HDAC2) expression and increased p27 (an important cell cycle inhibitor) expression in vitro and in vivo. The promoting effects of USP5 overexpression on cell proliferation and cell cycle transition, as well as the inhibitory effects of USP5 overexpression on p27 expression were mediated by HDAC2. Moreover, USP5 interacted with HDAC2, and disruption of USP5 enhanced the ubiquitination of HDAC2. HDAC2 protein was positively correlated USP5 protein, and negatively correlated with p27 protein in ovarian serous carcinomas tissues. Collectively, our data suggest the oncogenic function of USP5 and the potential regulatory mechanisms in ovarian carcinogenesis.

USP5 Promotes Uterine Corpus Endometrial Carcinoma Cell Growth and Migration via mTOR/4EBP1 Activation

“…[26][27][28] Apart from them, a growing body of evidence has demonstrated the tumor-promoting role of USP5 in different cancer types. 8,10,11,[13][14][15] And in this study, we found that it was also the case in UCEC. When USP5 was knocked down, cell viability was significantly impeded accompanied with blockade of cell cycle transition and induction of apoptosis.…”

“…The Decease of USP5 Causes Cell Cycle Arrest and Apoptosis of UCEC Cells USP5 was shown to modulate cell cycle progression in pancreatic cancer and ovarian cancer. 14,15 To reveal the mechanisms underlying the repression of cell proliferation, we analyzed cell cycle distribution of UCEC cells after USP5 knockdown. We observed significant accumulations of Hec-1-B cells in G0/G1-phase transfected with USP5 siRNAs compared to control cells, and meanwhile obvious reductions in S-phase and G2/M-phase (Figure 4A).…”

Ubiquitin specific peptidase 5 enhances STAT3 signaling and promotes migration and invasion in Pancreatic Cancer

“…USP5 is one of the important members of USP family. USP5 have been reported as an oncoprotein in diverse cancers including myeloma 4 , non-small cell lung cancer 5 , hepatocellular carcinoma 6 , colorectal cancer 7 , ovarian cancer 8 and pancreatic cancer 9 . USP5 have been studied in the development of pancreatic cancer 9 , 10 .…”

USP5 Promotes Metastasis in Non-Small Cell Lung Cancer by Inducing Epithelial-Mesenchymal Transition via Wnt/β-Catenin Pathway

“…Along with the decrease in b-catenin expression by knocking down USP5, it is suggested that these beneficial effects of USP5 are involved in the upregulation of Wnt/b-catenin signaling. It has been reported that USP5 promotes tumor proliferation and tumorigenesis through the deubiquitination of histone deacetylase 2 (HDAC2) (Du et al, 2019) and b-catenin (Ma et al, 2018). Meanwhile, HDAC2, a histone deacetylase, decreases GSK-3b protein (Wang et al, 2016), likely by deacetylating its histone proteins, hence impairing its gene transcription.…”