Deubiquitinase PSMD14 enhances hepatocellular carcinoma growth and metastasis by stabilizing GRB2

Lv, Jie; Zhang, Sheng; Wu, Huita; Lü, Jing; Lu, Yuyan; Wang, Fuqiang; Zhao, Wenxiu; Zhan, Ping; Lu, Junjiang; Fang, Qinliang; Xie, Chengrong; Yin, Zhenyu

doi:10.1016/j.canlet.2019.10.025

Cited by 80 publications

(102 citation statements)

References 31 publications

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Section: Seven Genes Expression Is Correlated With Immune Infiltratiosupporting

confidence: 82%

“…We analyzed the correlation between seven prognostic genes (PSMD14, RBM45, PSMD1, OLA1, including HCC, esophageal cancer, breast cancer [5,[12][13]. Our results are in accordance with these studies, implying that PSMD14 could be a potential prognostic gene for HCC [5]. To our knowledge, the expression of PSMD14 and its potential immune prognostic impact on HCC has not yet been explored, the potential immune prognostic role of PSMD14 and its associated genes in HCC was the focus on the present study.…”

Section: Seven Genes Expression Is Correlated With Immune Infiltratiomentioning

confidence: 99%

“…The deubiquitinase (DUB) 26S proteasome non-ATPase regulatory subunit 14 (PSMD14, RPN11 or POH1), belongs to the JAMM domain metalloprotease family of DUBs and is an important part of 19S regulatory cap in 26S proteasome [5]. PSMD14 has been confirmed to play vital roles in gene ontology and related pathway, including protein stability [6], tumour formation [7], transcriptional regulation [8], double-strand DNA break repair [9], senescence [10], apoptosis and resistance [11], growth and metastasis [5], BMP6 signaling [6], TGF-β signaling [8]. Recently, PSMD14 has been overexpressed in many human cancers, such as HCC, colorectal cancer, multiple myeloma, esophageal squamous cell carcinoma and breast cancer, which it This is related to the poor prognosis of the patients [5,6,[11][12][13].…”

Section: Introductionmentioning

confidence: 99%

“…PSMD14 has been confirmed to play vital roles in gene ontology and related pathway, including protein stability [6], tumour formation [7], transcriptional regulation [8], double-strand DNA break repair [9], senescence [10], apoptosis and resistance [11], growth and metastasis [5], BMP6 signaling [6], TGF-β signaling [8]. Recently, PSMD14 has been overexpressed in many human cancers, such as HCC, colorectal cancer, multiple myeloma, esophageal squamous cell carcinoma and breast cancer, which it This is related to the poor prognosis of the patients [5,6,[11][12][13]. PSMD14 acts as an oncogene that promotes tumor progression by deubiquitinating of different protein substrates.…”

Section: Introductionmentioning

confidence: 99%

“…For example, Deubiquitinase PSMD14 acts as a positive regulator for the initiation of the BMP6 signalling pathway, resulting in increased stability of the ALK2, either PSMD14 or ALK2 depletion significantly decreases colorectal cancer growth and chemoresistance [6]. Similarly, PSMD14 inhibits degradation of GRB2 by deubiquitinating this oncoprotein and stabilizing GRB2, which it enhances hepatocellular carcinoma growth and metastasis [5]. POH1 deubiquitinates the TGF-β receptors and CAV1, contributes to hyperactivation of TGF-β signaling and facilitates hepatocellular carcinoma metastasis, which it negatively regulates lysosome pathway-mediated turnover of TGF-β receptors [8].…”

Section: Introductionmentioning

confidence: 99%

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Immune prognostic implications of PSMD14 and its associated genes signatures in hepatocellular carcinoma

Tian

Abudoureyimu

Lin

et al. 2020

Preprint

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Background PSMD14 played a vital roles initiation and progression of hepatocellular carcinoma (HCC). However, PSMD14 and its-related genes for the immune prognostic implications of HCC patients have rarely been analyzed. Therefore, we aimed to explore gene signatures and immune prognostic values of PSMD14 and its-related genes in HCC. Method Analyzed the expression of PSMD14 in multiple databases, and clinicopathologic characteristics associated with PSMD14 overall survival using Wilcoxon signed-ranktest, logistic and Cox regression, Kaplan-Meier method. An immune prognostic signature (including RBM45, PSMD1, OLA1, CCT6A, LCAT and IVD) was constructed and validated using the co-expression and cox regression analyses in TCGA, ICGC and TIMER datasets. Gene Set Enrichment Analysis (GSEA) was performed using TCGA data set. Results Increased PSMD14 expression in HCC was significantly associated with poor prognosis and clinicopathologic characteristics (grade, histologic stage, surgical approach and T stage, all p-values < 0.05). A total of six PSMD14-related genes were detected, which markedly related to overall survival and immune infiltrating levels in HCC patients. Using cox regression analysis, the PSMD14 and its-related genes were found to be an independent prognostic factor for HCC survival. Calibration curves confirmed good consistency between clinical nomogram prediction and actual observation. Immune prognostic model suggests that patients in the high‐risk group shown significantly poorer survival than patients in the low‐risk group. Conclusion We screened potential immune prognostic genes and constructed and verified a novel PSMD14-based prognostic model of HCC, which provides new potential prognostic biomarkers and therapeutic targets and lays a theoretical foundation for immunotherapy of HCC.

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Section: Seven Genes Expression Is Correlated With Immune Infiltratiosupporting

confidence: 82%

Section: Seven Genes Expression Is Correlated With Immune Infiltratiomentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Immune prognostic implications of PSMD14 and its associated genes signatures in hepatocellular carcinoma

Tian

Abudoureyimu

Lin

et al. 2020

Preprint

View full text Add to dashboard Cite

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Deubiquitinase PSMD14 promotes ovarian cancer progression by decreasing enzymatic activity of PKM2

Sun

Liu

et al. 2021

Molecular Oncology

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Dysregulation of deubiquitination has been reported to contribute to carcinogenesis. However, the function and mechanism of deubiquitinating enzyme 26S proteasome non-ATPase regulatory subunit 14 (PSMD14) in the progression of ovarian cancer (OV), the deadliest gynecological cancer, still remains to be characterized. The present study demonstrated that PSMD14 was overexpressed in OV tissues and its higher levels correlated with a higher International Federation of Gynecology and Obstetrics (FIGO) stage in OV patients. A high level of PSMD14 expression was related to poor survival in OV patients. Knockdown and overexpression experiments elucidated that PSMD14 stimulated OV cell proliferation, invasion, and migration in vitro. Repression of PSMD14 suppressed OV tumor growth in vivo. PSMD14 inhibitor O-phenanthroline (OPA) effectively attenuated malignant behaviors of OV cells in vitro and OV tumor growth in vivo. Mechanistically, we uncovered that PSMD14 was involved in post-translational regulation of pyruvate kinase M2 isoform (PKM2). PSMD14 decreased K63-linked ubiquitination on PKM2, downregulated the ratio of PKM2 tetramers to dimers and monomers, and subsequently diminished pyruvate kinase activity and induced nuclear translocation of PKM2, contributing to aerobic glycolysis in OV cells. Collectively, our findings highlight the potential roles of PSMD14 as a biomarker and therapeutic candidate for OV.

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Identification of PSMD14 as a potential novel prognosis biomarker and therapeutic target for osteosarcoma

Yang

Wei

2021

Cancer Reports

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Background: Osteosarcoma is the most common primary bone tumor. The survival rate of osteosarcoma patients has not significantly increased in the past decades.Uncovering the mechanisms of malignancy, progression, and metastasis will shed light on the development of new therapeutic targets and treatment for osteosarcoma. Aim:The aim of this study is to identify potential osteosarcoma biomarker and/or therapeutic targets by using integrated bioinformatics analysis. Methods and results:We utilized existing gene expression datasets to identify differential expressed genes (DEGs) that could serve as osteosarcoma biomarkers or even as therapeutic targets. We found 48 DEGs were overlapped in three datasets. Among these 48 DEGs, PSMD14 was on the top of the up-regulated gene list. We further found that higher PSMD14 expression was correlated with higher risk group (younger age group, ≤20.83 years of age), metastasis within 5 years and higher grade of tumor. Higher PSMD14 expression in osteosarcoma had positive correlation with higher infiltration of CD8+ T cells, neutrophils and myeloid dendritic cells. Kaplan-Myer survival data further revealed that higher expression of PSMD14 predicted significantly worse prognosis (p = .013). Gene set enrichment analysis was further performed for the DEGs related to PSMD14 in osteosarcoma. We found that lower PSMD14 expression group had more immune responses such as interferon γ, α responses, inflammation response etc. However, the higher PSMD14 expression group had more cell proliferation-related biological processes, such as G2M checkpoints and Myc targets. Through establishing protein-protein interaction networks using PSMD14 related DEGs, we identified 10 hub genes that were all ribosomal proteins. These hub genes may play roles in osteosarcoma tumorigenesis, progression and/or metastasis. Conclusion:We identified PSMD14 gene as a possible osteosarcoma biomarker, and/or a possible therapeutic target.

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Deubiquitinase PSMD14 enhances hepatocellular carcinoma growth and metastasis by stabilizing GRB2

Cited by 80 publications

References 31 publications

Immune prognostic implications of PSMD14 and its associated genes signatures in hepatocellular carcinoma

Immune prognostic implications of PSMD14 and its associated genes signatures in hepatocellular carcinoma

Deubiquitinase PSMD14 promotes ovarian cancer progression by decreasing enzymatic activity of PKM2

Identification of PSMD14 as a potential novel prognosis biomarker and therapeutic target for osteosarcoma

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