The expression of ubiquitin‐specific peptidase 8 and its prognostic role in patients with breast cancer

Han, Qian; Kong, Jun Suk; Cheng, Yafang; Li, Gang

doi:10.1002/jcb.27337

Cited by 23 publications

(12 citation statements)

References 41 publications

(86 reference statements)

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“…13 Notably, the activity of DUBs directly affects the turnover rate, activity, regeneration and localization of various proteins in cells. 14 Among these DUBs, ubiquitin-specific protease 8 (USP8) was demonstrated to be involved in breast cancer, 15,16 lung cancer, 17 corticotroph adenomas 18,19 and pituitary adenomas, 19,20 and these studies suggested that USP8 played an important role in different types of cancer. Nevertheless, no study has reported the impact of USP8 on GC.…”

Section: Introductionmentioning

confidence: 99%

USP8 Inhibitor Suppresses HER-2 Positive Gastric Cancer Cell Proliferation and Metastasis via the PI3K/AKT Signaling Pathway

Sun

Shen

Zheng

et al. 2020

OTT

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Referring to global cancer statistics, the incidence of gastric cancer (GC) was ranked sixth; however, detailed mechanisms underlying its development were not thoroughly investigated. Previous studies have reported that inhibition of ubiquitin-specific peptidase 8 (USP8) induced degradation of several receptor tyrosine kinases, such as epidermal growth factor receptor (EGFR), embryonic stem cells (ESCs), etc. Nevertheless, the regulation of HER-2 by USP8 and the molecular mechanisms controlling their role in the pathogenesis of GC remain unknown. Patients and Methods: A total of 69 patients with histologically confirmed GC were recruited to satisfy the purpose of this study. Initially, tumor samples and GC cell lines were used to detect USP8 and HER-2 levels. Next, MTT and colony formation assays were applied to analyze cell proliferation capability. Cell migration and invasion ability were examined by transwell assays. To examine related mRNA and protein expressions, Western blot assays and quantitative real-time PCR (qRT-PCR) were performed. Immunofluorescence was used to detect the effect of USP8 inhibitor on GC cells. Finally, in vivo experiments were used to examine the effect of USP8 inhibitor. Results: Patients with USP8 high-expression tumors have shown worse overall survival while opposite results found in patients with low USP8 expressions. Regarding disease prognosis, patients with low expression of USP8 and HER-2 were performed better prognosis, whereas those with overexpression of USP8 and HER-2 shown poor prognosis. USP8 inhibitor significantly inhibited HER-2 positive cell NCI-N87 proliferation and metastasis. In addition, USP8 stabilizes HER-2, preventing it from ubiquitin proteasome-mediated degradation. In vivo studies confirmed that the USP8 inhibitor inhibited HER-2 positive cell NCI-N87 tumor growth. However, it did not affect the HER2-negative cell MGC-803. Careful investigation unraveled that the USP8 inhibitor significantly inhibited NCI-N87 cell proliferation and metastasis via phosphatidylinositol-3-kinases/protein-serine-threonine kinase (PI3K/AKT) pathway. Conclusion: The USP8 inhibited HER-2 positive GC cell proliferation and migration in vivo and in vitro and probably served as a novel potential therapeutic biomarker for HER-2 positive GC.

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Section: Introductionmentioning

confidence: 99%

USP8 Inhibitor Suppresses HER-2 Positive Gastric Cancer Cell Proliferation and Metastasis via the PI3K/AKT Signaling Pathway

Sun

Shen

Zheng

et al. 2020

OTT

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“…In contrast to most tumors in which immunode cient tumor environment is associated with less favorable tumor behavior [44], CTAs with USP8 mutation and "cold" iTME are smaller in size [16] and have high remission rates after surgery [17,20,21]. Our ndings suggest that the favorable outcome of patients with USP8-mutated corticotroph adenomas is not immune-response dependent.…”

Section: Discussionmentioning

confidence: 72%

“…USP8 was also studied in the context of several other tumors. In breast cancer, high expression of USP8 was associated with better outcomes [21]. However, expression of USP8 in lung adenocarcinoma [22] and cervical squamous cell carcinoma [23] was associated with poorer outcomes compared with USP8negative tumors.…”

Section: Introductionmentioning

confidence: 99%

USP8 Status Affects the Immune Landscape of Corticotroph Pituitary Adenomas

Greidinger¹,

Mor‐Cohen²,

Zemet³

et al. 2021

Preprint

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Purpose Activating somatic mutations in ubiquitin-specific protease-8 (USP8), encoding a deubiquitinating protein, are found in approximately 30% of corticotroph-derived pituitary adenomas (CPA). USP8 has immunomodulating properties that were demonstrated in non-tumoral diseases. Our study aims to assess the influence of USP8 mutation status on the immune tumor microenvironment (iTME) of CPAs. Methods We analyzed 20 PCAs by RNA sequencing. In six of them, USP8 mutations were detected. We assessed the immune landscape of tumors by quantifying 22 immune cell types based on the CIBERSORT transcriptome signature-recognition algorithms. Also, we performed a pathway analysis for genes that were differentially expressed between groups using the Wikipathways 2019 and Reactome 2016 databases and using the EnrichR platform results. Results CPA with activating USP8 mutations were associated with "cold" iTME compared with wild type USP8 CPA. This "cold" iTME was reflected by lower fractions of B cells, CD4, regulatory and gamma/delta T cells, natural killer cells, M0 and M1 macrophages, dendritic cells and eosinophils (p < 0.05 for all comparisons). Pathways altered by the presence of USP8 mutation, based on the most differentially expressed genes (3,061 genes) included Microglia Pathogen Phagocytosis and multiple toll-like receptor signaling pathways (p < 0.0001). Conclusion USP8 status affects the immune landscape of corticotroph pituitary adenomas, with USP8 mutation associated with "cold" iTME.

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“…17 However, USP8 is down-regulated in breast cancer tissues, compared with that in normal breast tissues, and the high-expression of USP8 is correlated with better clinical features of breast cancer patients. 18 The reasons for the difference among these studies remained to be elucidated. The expression difference of USP8 in NSCLC tissues and normal tissues, as well as the correlation analysis with clinical characteristics of NSCLC patients, are also our future research directions.…”

Section: Discussionmentioning

confidence: 99%

Knockdown of USP8 Inhibits the Growth of Lung Cancer Cells

Rong¹,

Zhu²,

Cai³

et al. 2020

CMAR

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Purpose: Lung cancer is the deadliest tumor in the world. This study aimed to investigate the effection of USP8 on the proliferation and growth of NSCLC cells. Methods: The proliferation, migration, invasion, cell cycle progression, and apoptosis of A549 and H1299 cells were evaluated with CCK8, colony formation, scratch, transwell, and flow cytometry experiments. Furthermore, the expression of cell cycle-and apoptosis-related proteins was detected by western blot. Results: Knockdown of USP8 inhibited the proliferation, migration, invasion, and cell cycle progression of A549 and H1299 cells, and promoted the apoptosis. The results of western blot indicated that knockdown of USP8 down-regulated the expression of Cyclin D1, CDK4, CDK6, p-AKT, and Bcl2, and up-regulated the expression of Bax. Conclusion: Knockdown of USP8 inhibited the proliferation of human lung cancer cells by regulating cell cycle-and apoptosis-related proteins. USP8 may be a therapeutic target for lung cancer.

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The expression of ubiquitin‐specific peptidase 8 and its prognostic role in patients with breast cancer

Abstract: Our results demonstrated that USP8 might predict better clinical characteristics and might be a protective factor for patients with BC.

Cited by 23 publications

References 41 publications

<p>USP8 Inhibitor Suppresses HER-2 Positive Gastric Cancer Cell Proliferation and Metastasis via the PI3K/AKT Signaling Pathway</p>

<p>USP8 Inhibitor Suppresses HER-2 Positive Gastric Cancer Cell Proliferation and Metastasis via the PI3K/AKT Signaling Pathway</p>

USP8 Status Affects the Immune Landscape of Corticotroph Pituitary Adenomas

<p>Knockdown of USP8 Inhibits the Growth of Lung Cancer Cells</p>

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