Ubiquitin-specific protease 2a promotes hepatocellular carcinoma progression via deubiquitination and stabilization of RAB1A

Xiong, Bin; Huang, Jun; Liu, Yan; Zou, Min; Zhang, Zhibo; Gong, Jianping; Wu, Xiaoling; Qiu, Chao

doi:10.1007/s13402-020-00568-8

Cited by 17 publications

(13 citation statements)

References 38 publications

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“…For example, deubiquitinating enzymes (DUBs) play a role in cleaving the Ub chain and decreasing the ubiquitination of substrates in the cancer cells. It has been reported that USP2a, USP7, USP21, and USP22 are highly expressed in the HCC tissue or cells and promote tumor development ( Cai et al, 2015 ; Li et al, 2018 ; Ling et al, 2020 ; Xiong et al, 2021 ). However, further study is needed to reveal the mechanism in the HCC cells.…”

Section: Discussionmentioning

confidence: 99%

Differential Degradation of TRA2A and PYCR2 Mediated by Ubiquitin E3 Ligase E4B

Jiang

Peng

et al. 2022

Front. Cell Dev. Biol.

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E4B belongs to the U-box E3 ligase family and functions as either an E3 or an E4 enzyme in protein ubiquitination. Transformer2A (TRA2A) and Pyrroline-5-carboxylate reductase 2 (PYCR2) are related to cancer development and are overexpressed in many cancer cells. The degradation of TRA2A and PYCR2 mediated by the ubiquitin-proteasome system (UPS) has not been reported. This study validated that E4B could ubiquitinate TRA2A and PYCR2 as an E3 ligase both in vitro and in the HEK293 cells. E4B mediated the degradation by forming K11- and K48- linked polyubiquitin chains on TRA2A and PYCR2, respectively. E4B regulated the alternative splicing function of TRA2A and affected RSRC2 transcription in the HEK293 cells. Although E4B is highly expressed, it hardly degrades TRA2A and PYCR2 in hepatocellular carcinoma (HCC) cells, suggesting other mechanisms exist for degradation of TRA2A and PYCR2 in the HCC cells. We finally reported that E4B interacted with substrates via its variable region.

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Section: Discussionmentioning

confidence: 99%

Differential Degradation of TRA2A and PYCR2 Mediated by Ubiquitin E3 Ligase E4B

Jiang

Peng

et al. 2022

Front. Cell Dev. Biol.

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“…Upregulated USP2a expression in high-grade tumors corresponds to lymph node metastasis in breast cancer 26. USP2a can also promote hepatocellular carcinoma progression through deubiquitination and stabilization of RAB1A 27. Therefore, USP2a is involved in nearly all types of cancers, including UTUC.…”

Section: Discussionmentioning

confidence: 99%

“…26 USP2a can also promote hepatocellular carcinoma progression through deubiquitination and stabilization of RAB1A. 27 Therefore, USP2a is involved in nearly all types of cancers, including UTUC.…”

Section: Discussionmentioning

confidence: 99%

High Ubiquitin-Specific Protease 2a Expression Level Predicts Poor Prognosis in Upper Tract Urothelial Carcinoma

Lee²,

et al. 2022

Applied Immunohistochemistry &Amp; Molecular Morphology

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Background: Ubiquitin-mediated protein degradation has been reported to be involved in regulating the activity of oncoproteins and tumor suppressors. Dysfunction or dysregulation of the ubiquitin-proteasome system may induce tumorigenesis. Deubiquitinase ubiquitin-specific protease 2a (USP2a) has been reported to regulate cell growth or death and is involved in the pathogenesis of various diseases, including cancers. However, the role of USP2a in upper tract urothelial carcinoma (UTUC) has not been investigated yet. The goal of this study was to evaluate the clinical significance of USP2a expression in UTUC.Materials and Methods: A total of 110 UTUC cases were included in this study. USP2a expression level was evaluated through immunohistochemistry staining, and the correlation of USP2a expression level with both clinical and pathologic variables was analyzed.Results: High USP2a expression level was observed in 48 (43.6%) cancer specimens. USP2a expression level was significantly correlated with tumor stage (P = 0.001), grade (P = 0.033), and tumor recurrence (P = 0.008). High USP2a expression level was correlated with poor disease-free survival (P = 0.005) and cancerspecific survival (P < 0.001). In addition, high USP2a expression level was an independent predictor of poor disease-free survival (hazard ratio = 2.31; P = 0.007) and cancer-specific survival (hazard ratio = 5.49; P = 0.009).Conclusions: This study indicated that USP2a protein expression level may be a potential biomarker for predicting UTUC patient survival. Further prospective studies are needed to investigate the role of USP2a in UTUC progression.

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“…Allende-Vega further illustrated this mechanism that ectopic expression of USP2a causes accumulation of Mdm2 and promotes Mdm2-mediated p53 degradation ( 35 ). USP2a could promote hepatocellular carcinoma invasion via deubiquitinating RAB1A ( 36 ). These studies indicated USP2a presented oncogenic properties ( 34 , 37 , 38 ).…”

Section: Discussionmentioning

confidence: 99%

Decreased USP2a Expression Inhibits Trophoblast Invasion and Associates With Recurrent Miscarriage

et al. 2021

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An appropriate development of the placenta consisting of trophoblast cell migration, invasion, proliferation, and apoptosis, is essential to establishing and maintaining a successful pregnancy. Ubiquitin‐specific protease 2a (USP2a) regulates the processes of metastasis in multiple tumor cells. Yet, no known research has focused on exploring the effect of USP2a on trophoblasts and its possible mechanism in the pathogenies of recurrent miscarriage (RM). In this study, we first detected the decreased mRNA levels and the protein levels of USP2a in placental villous tissue samples from the RM patients. In vitro assays verified that overexpression of USP2a promoted human trophoblast proliferation, migration, invasion, whereas knockdown of USP2a inhibited these processes. Mechanistically, USP2a activated PI3K/Akt/GSK3β signaling pathway to promote nuclear translocation of β‐catenin and further activated epithelial-mesenchymal transition (EMT) in the trophoblasts. Moreover, transforming growth factor-beta (TGF-β) up-regulated USP2a expression in trophoblasts. Interestingly, M2 macrophage secreted TGF-β induced trophoblast migration and invasion, and an anti-TGF-β antibody alleviated this effect. Collectively, this study indicated that USP2a regulated trophoblast invasion and that abnormal USP2a expression might lead to aberrant trophoblast invasion, thus contributing to RM.

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Ubiquitin-specific protease 2a promotes hepatocellular carcinoma progression via deubiquitination and stabilization of RAB1A

Cited by 17 publications

References 38 publications

Differential Degradation of TRA2A and PYCR2 Mediated by Ubiquitin E3 Ligase E4B

Differential Degradation of TRA2A and PYCR2 Mediated by Ubiquitin E3 Ligase E4B

High Ubiquitin-Specific Protease 2a Expression Level Predicts Poor Prognosis in Upper Tract Urothelial Carcinoma

Decreased USP2a Expression Inhibits Trophoblast Invasion and Associates With Recurrent Miscarriage

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