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We are analyzing https://link.springer.com/article/10.1186/s12964-019-0480-x.

Title:
Ubiquitin-specific protease 22 is critical to in vivo angiogenesis, growth and metastasis of non-small cell lung cancer | Cell Communication and Signaling
Description:
Background Loss of monoubiquitination of histone H2B (H2Bub1) was found to be associated with poor differentiation, cancer stemness, and enhanced malignancy of non-small cell lung cancer (NSCLC). Herein, we investigated the biological significance and therapeutic implications of ubiquitin-specific protease 22 (USP22), an H2Bub1 deubiquitinase, in non-small cell lung cancer (NSCLC). Methods USP22 expression and its clinical relevance were assessed in NSCLC patients. The effects of USP22 knockout on sensitivity to cisplatin and irradiation, and growth, metastasis of NSCLC xenografts, and survival of cancer-bearing mice were investigated. The underlying mechanisms of targeting USP22 were explored. Results Overexpression of USP22 was observed in 49.0% (99/202) of NSCLC tissues; higher USP22 immunostaining was found to be associated with enhanced angiogenesis and recurrence of NSCLC. Notably, USP22 knockout dramatically suppressed in vitro proliferation, colony formation; and angiogenesis, growth, metastasis of A549 and H1299 in mouse xenograft model, and significantly prolonged survival of metastatic cancer-bearing mice. Furthermore, USP22 knockout significantly impaired non-homologous DNA damage repair capacity, enhanced cisplatin and irradiation-induced apoptosis in these cells. In terms of underlying mechanisms, RNA sequencing and gene ontology enrichment analysis demonstrated that USP22 knockout significantly suppressed angiogenesis, proliferation, EMT, RAS, c-Myc pathways, concurrently enhanced oxidative phosphorylation and tight junction pathways in A549 and H1299 NSCLC cells. Immunoblot analysis confirmed that USP22 knockout upregulated E-cadherin, p16; reduced ALDH1A3, Cyclin E1, c-Myc, and attenuated activation of AKT and ERK pathways in these cells. Conclusions Our findings suggest USP22 plays critical roles in the malignancy and progression of NSCLC and provide rationales for targeting USP22, which induces broad anti-cancer activities, as a novel therapeutic strategy for NSCLC patient.
Website Age:
28 years and 1 months (reg. 1997-05-29).

Matching Content Categories {๐Ÿ“š}

  • Science
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Custom-built

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๐ŸŒ  Phenomenal Traffic: 5M - 10M visitors per month


Based on our best estimate, this website will receive around 5,000,019 visitors per month in the current month.
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How Does Link.springer.com Make Money? {๐Ÿ’ธ}

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Keywords {๐Ÿ”}

usp, cancer, cells, pubmed, lung, fig, cell, article, nsclc, knockout, parent, google, scholar, analysis, cas, panel, significantly, metastasis, found, mice, angiogenesis, hbub, data, tissues, central, signaling, growth, cisplatin, gene, cancers, pathways, study, progression, repair, protein, tumor, vivo, dna, zhang, expression, proliferation, metastatic, survival, ihc, compared, wang, irradiation, apoptotic, apoptosis, adenocarcinoma,

Topics {โœ’๏ธ}

nod/scid/il2rgamma null mice spt-ada-gcn5-acetyltransferase sirt1 spt-ada-gcn5-acetyltransferase dna double-strand breaks efficient dot1-mediated methylation class switch recombination article download pdf fluorescence-activated cell sorting metastatic cancer-bearing nsgย mice microvessel density dnapk-mediated gammah2ax formation monoclonal anti-usp22 antibody cadherin-catenin adhesion system ubiquitinase rnf20/rnf40 complex small-cell lung cancer ubiquitin-specific peptidase 22 growth-promoting oncogenes including sensitize cancer cells express i-scel endonuclease brca-parp synthetic lethality kaplan-meier survival curves phprt-drgfp reporter plasmid kaplan-meier analysis shows small-cell lung cancers full access metastatic cancer-bearing mice c-myc signaling pathways ubiquitin-specific protease 22 central mechanism responsible endothelial cell marker rnf20/rnf40 dependent h2bub1 mono-ubiquitin moiety tdtomato protein-positive cells crispr/cas9ย system h1299-usp22โˆ’/โˆ’ cancer cells usp22โˆ’/โˆ’h1299 cancer cells a549 cancer-bearing mice p-akt signaling pathway original rna-seq data rna-seq data analysis dna damage repair immunostaining endothelial cells histone h2b monoubiquitination usp22 knockout impaired usp22โˆ’/โˆ’ versus usp22+/+ blood vessel density usp22 knockout impairs privacy choices/manage cookies differentially expressed proteins related subjects

Schema {๐Ÿ—บ๏ธ}

WebPage:
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         headline:Ubiquitin-specific protease 22 is critical to in vivo angiogenesis, growth and metastasis of non-small cell lung cancer
         description:Loss of monoubiquitination of histone H2B (H2Bub1) was found to be associated with poor differentiation, cancer stemness, and enhanced malignancy of non-small cell lung cancer (NSCLC). Herein, we investigated the biological significance and therapeutic implications of ubiquitin-specific protease 22 (USP22), an H2Bub1 deubiquitinase, in non-small cell lung cancer (NSCLC). USP22 expression and its clinical relevance were assessed in NSCLC patients. The effects of USP22 knockout on sensitivity to cisplatin and irradiation, and growth, metastasis of NSCLC xenografts, and survival of cancer-bearing mice were investigated. The underlying mechanisms of targeting USP22 were explored. Overexpression of USP22 was observed in 49.0% (99/202) of NSCLC tissues; higher USP22 immunostaining was found to be associated with enhanced angiogenesis and recurrence of NSCLC. Notably, USP22 knockout dramatically suppressed in vitro proliferation, colony formation; and angiogenesis, growth, metastasis of A549 and H1299 in mouse xenograft model, and significantly prolonged survival of metastatic cancer-bearing mice. Furthermore, USP22 knockout significantly impaired non-homologous DNA damage repair capacity, enhanced cisplatin and irradiation-induced apoptosis in these cells. In terms of underlying mechanisms, RNA sequencing and gene ontology enrichment analysis demonstrated that USP22 knockout significantly suppressed angiogenesis, proliferation, EMT, RAS, c-Myc pathways, concurrently enhanced oxidative phosphorylation and tight junction pathways in A549 and H1299 NSCLC cells. Immunoblot analysis confirmed that USP22 knockout upregulated E-cadherin, p16; reduced ALDH1A3, Cyclin E1, c-Myc, and attenuated activation of AKT and ERK pathways in these cells. Our findings suggest USP22 plays critical roles in the malignancy and progression of NSCLC and provide rationales for targeting USP22, which induces broad anti-cancer activities, as a novel therapeutic strategy for NSCLC patient.
         datePublished:2019-12-16T00:00:00Z
         dateModified:2019-12-16T00:00:00Z
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            Non-small cell lung cancer (NSCLC)
            USP22
            Angiogenesis
            Epithelial-mesenchymal transition (EMT)
            Growth
            Metastasis
            Therapeutic target
            Cell Biology
            Protein-Ligand Interactions
            Receptors
            Cytokines and Growth Factors
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      headline:Ubiquitin-specific protease 22 is critical to in vivo angiogenesis, growth and metastasis of non-small cell lung cancer
      description:Loss of monoubiquitination of histone H2B (H2Bub1) was found to be associated with poor differentiation, cancer stemness, and enhanced malignancy of non-small cell lung cancer (NSCLC). Herein, we investigated the biological significance and therapeutic implications of ubiquitin-specific protease 22 (USP22), an H2Bub1 deubiquitinase, in non-small cell lung cancer (NSCLC). USP22 expression and its clinical relevance were assessed in NSCLC patients. The effects of USP22 knockout on sensitivity to cisplatin and irradiation, and growth, metastasis of NSCLC xenografts, and survival of cancer-bearing mice were investigated. The underlying mechanisms of targeting USP22 were explored. Overexpression of USP22 was observed in 49.0% (99/202) of NSCLC tissues; higher USP22 immunostaining was found to be associated with enhanced angiogenesis and recurrence of NSCLC. Notably, USP22 knockout dramatically suppressed in vitro proliferation, colony formation; and angiogenesis, growth, metastasis of A549 and H1299 in mouse xenograft model, and significantly prolonged survival of metastatic cancer-bearing mice. Furthermore, USP22 knockout significantly impaired non-homologous DNA damage repair capacity, enhanced cisplatin and irradiation-induced apoptosis in these cells. In terms of underlying mechanisms, RNA sequencing and gene ontology enrichment analysis demonstrated that USP22 knockout significantly suppressed angiogenesis, proliferation, EMT, RAS, c-Myc pathways, concurrently enhanced oxidative phosphorylation and tight junction pathways in A549 and H1299 NSCLC cells. Immunoblot analysis confirmed that USP22 knockout upregulated E-cadherin, p16; reduced ALDH1A3, Cyclin E1, c-Myc, and attenuated activation of AKT and ERK pathways in these cells. Our findings suggest USP22 plays critical roles in the malignancy and progression of NSCLC and provide rationales for targeting USP22, which induces broad anti-cancer activities, as a novel therapeutic strategy for NSCLC patient.
      datePublished:2019-12-16T00:00:00Z
      dateModified:2019-12-16T00:00:00Z
      pageStart:1
      pageEnd:17
      license:http://creativecommons.org/publicdomain/zero/1.0/
      sameAs:https://doi.org/10.1186/s12964-019-0480-x
      keywords:
         Non-small cell lung cancer (NSCLC)
         USP22
         Angiogenesis
         Epithelial-mesenchymal transition (EMT)
         Growth
         Metastasis
         Therapeutic target
         Cell Biology
         Protein-Ligand Interactions
         Receptors
         Cytokines and Growth Factors
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      author:
            name:Keqiang Zhang
            url:http://orcid.org/0000-0002-4210-4401
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                  address:
                     name:The Integrative Genomics Core Laboratory of Department of Molecular Medicine, City of Hope National Medical Center, Duarte, USA
                     type:PostalAddress
                  type:Organization
            type:Person
            name:Ting Sun
            affiliation:
                  name:City of Hope National Medical Center
                  address:
                     name:Division of Thoracic Surgery, City of Hope National Medical Center, Duarte, USA
                     type:PostalAddress
                  type:Organization
                  name:the General Hospital of Ningxia Medical University
                  address:
                     name:Department of Surgery, the General Hospital of Ningxia Medical University, Yinchuan, China
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            name:Yuming Guo
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                  address:
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                     type:PostalAddress
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            name:Ravi Salgia
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                  address:
                     name:Division of Thoracic Surgery, City of Hope National Medical Center, Duarte, USA
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      affiliation:
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               name:Division of Thoracic Surgery, City of Hope National Medical Center, Duarte, USA
               type:PostalAddress
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      email:[email protected]
      name:Lu Yang
      affiliation:
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            address:
               name:Department of System Biology, City of Hope National Medical Center, Duarte, USA
               type:PostalAddress
            type:Organization
      name:Jinhui Wang
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            name:City of Hope National Medical Center
            address:
               name:The Integrative Genomics Core Laboratory of Department of Molecular Medicine, City of Hope National Medical Center, Duarte, USA
               type:PostalAddress
            type:Organization
      name:Ting Sun
      affiliation:
            name:City of Hope National Medical Center
            address:
               name:Division of Thoracic Surgery, City of Hope National Medical Center, Duarte, USA
               type:PostalAddress
            type:Organization
            name:the General Hospital of Ningxia Medical University
            address:
               name:Department of Surgery, the General Hospital of Ningxia Medical University, Yinchuan, China
               type:PostalAddress
            type:Organization
      name:Yuming Guo
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            name:City of Hope National Medical Center
            address:
               name:Division of Comparative Medicine, City of Hope National Medical Center, Duarte, USA
               type:PostalAddress
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            address:
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               type:PostalAddress
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      name:Tommy R. Tong
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            name:City of Hope National Medical Center
            address:
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               type:PostalAddress
            type:Organization
      name:Rajendra Pangeni
      affiliation:
            name:City of Hope National Medical Center
            address:
               name:Division of Thoracic Surgery, City of Hope National Medical Center, Duarte, USA
               type:PostalAddress
            type:Organization
      name:Ravi Salgia
      affiliation:
            name:City of Hope National Medical Center
            address:
               name:Department of Medical Oncology & Therapeutics Research, City of Hope National Medical Center, Duarte, USA
               type:PostalAddress
            type:Organization
      name:Dan J. Raz
      affiliation:
            name:City of Hope National Medical Center
            address:
               name:Division of Thoracic Surgery, City of Hope National Medical Center, Duarte, USA
               type:PostalAddress
            type:Organization
      email:[email protected]
PostalAddress:
      name:Division of Thoracic Surgery, City of Hope National Medical Center, Duarte, USA
      name:Department of System Biology, City of Hope National Medical Center, Duarte, USA
      name:The Integrative Genomics Core Laboratory of Department of Molecular Medicine, City of Hope National Medical Center, Duarte, USA
      name:Division of Thoracic Surgery, City of Hope National Medical Center, Duarte, USA
      name:Department of Surgery, the General Hospital of Ningxia Medical University, Yinchuan, China
      name:Division of Comparative Medicine, City of Hope National Medical Center, Duarte, USA
      name:Department of Pathology, City of Hope National Medical Center, Duarte, USA
      name:Division of Biostatistics, City of Hope National Medical Center, Duarte, USA
      name:Division of Thoracic Surgery, City of Hope National Medical Center, Duarte, USA
      name:Department of Medical Oncology & Therapeutics Research, City of Hope National Medical Center, Duarte, USA
      name:Division of Thoracic Surgery, City of Hope National Medical Center, Duarte, USA

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Libraries {๐Ÿ“š}

  • Clipboard.js
  • Knockout.js
  • Prism.js

CDN Services {๐Ÿ“ฆ}

  • Crossref

4.59s.