WTAP facilitates progression of hepatocellular carcinoma via m6A-HuR-dependent epigenetic silencing of ETS1 View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2019-08-22

AUTHORS

Yunhao Chen, Chuanhui Peng, Junru Chen, Diyu Chen, Beng Yang, Bin He, Wendi Hu, Yanpeng Zhang, Hua Liu, Longfei Dai, Haiyang Xie, Lin Zhou, Jian Wu, Shusen Zheng

ABSTRACT

BackgroundN6-methyladenosine (m6A) methylation, a well-known modification with new epigenetic functions, has been reported to participate in the tumorigenesis of hepatocellular carcinoma (HCC), providing novel insights into the molecular pathogenesis of this disease. However, as the key component of m6A methylation, Wilms tumor 1-associated protein (WTAP) has not been well studied in HCC. Here we investigated the biological role and underlying mechanism of WTAP in liver cancer.MethodsWe determined the expression of WTAP and its correlation with clinicopathological features using tissue microarrays and the Cancer Genome Atlas (TCGA) dataset. And we clarified the effects of WTAP on HCC cells using cell proliferation assay, colony formation, Edu assay and subcutaneous xenograft experiments. We then applied RNA sequencing combined with gene expression omnibus (GEO) data to screen candidate targets of WTAP. Finally, we investigated the regulatory mechanism of WTAP in HCC by m6A dot blot assay, methylated RNA immunoprecipitation (MeRIP) assay, dual luciferase reporter assay, RNA immunoprecipitation (RIP) assay and Chromatin immunoprecipitation (ChIP) assay.ResultsWe demonstrated that WTAP was highly expressed in HCC which indicated the poor prognosis, and that WTAP expression served as an independent predictor of HCC survival. Functionally, WTAP promoted the proliferation capability and tumor growth of HCC cells in vitro and in vivo. Furthermore, ETS proto-oncogene 1 (ETS1) was identified as the downstream effector of WTAP. The m6A modification regulated by WTAP led to post-transcriptional suppression of ETS1, with the implication of Hu-Antigen R (HuR) as an RNA stabilizer. Then ETS1 was found to inhibit the progression of HCC and could rescue the phenotype induced by WTAP deficiency. Moreover, WTAP modulated the G2/M phase of HCC cells through a p21/p27-dependent pattern mediated by ETS1.ConclusionWe have identified that WTAP is significantly up-regulated in HCC and promotes liver cancer development. WTAP-guided m6A modification contributes to the progression of HCC via the HuR-ETS1-p21/p27 axis. Our study is the first to report that WTAP-mediated m6A methylation has a crucial role in HCC oncogenesis, and highlights WTAP as a potential therapeutic target of HCC treatment. More... »

PAGES

127

References to SciGraph publications

  • 2013-11-27. N6-methyladenosine-dependent regulation of messenger RNA stability in NATURE
  • 2016-09-07. m6A RNA methylation promotes XIST-mediated transcriptional repression in NATURE
  • 2014-01-07. N6-methyladenosine modification destabilizes developmental regulators in embryonic stem cells in NATURE CELL BIOLOGY
  • 2018-02-27. Wilms’ tumor 1-associating protein promotes renal cell carcinoma proliferation by regulating CDK2 mRNA stability in JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH
  • 2018-08-24. Wilms’ tumor 1-associating protein plays an aggressive role in diffuse large B-cell lymphoma and forms a complex with BCL6 via Hsp90 in CELL COMMUNICATION AND SIGNALING
  • 2018-02-27. VIRMA mediates preferential m6A mRNA methylation in 3′UTR and near stop codon and associates with alternative polyadenylation in CELL DISCOVERY
  • 2017-01-20. YTHDF3 facilitates translation and decay of N6-methyladenosine-modified RNA in CELL RESEARCH
  • 2014-01-10. Mammalian WTAP is a regulatory subunit of the RNA N6-methyladenosine methyltransferase in CELL RESEARCH
  • 2016-05-25. Structural basis of N6-adenosine methylation by the METTL3–METTL14 complex in NATURE
  • 2016-11-30. m6A potentiates Sxl alternative pre-mRNA splicing for robust Drosophila sex determination in NATURE
  • 2014-09-21. Structural basis for selective binding of m6A RNA by the YTHDC1 YTH domain in NATURE CHEMICAL BIOLOGY
  • 2018-08-27. m6A mRNA methylation regulates AKT activity to promote the proliferation and tumorigenicity of endometrial cancer in NATURE CELL BIOLOGY
  • 2016-11-03. Post-transcriptional gene regulation by mRNA modifications in NATURE REVIEWS MOLECULAR CELL BIOLOGY
  • 2013-12-06. A METTL3–METTL14 complex mediates mammalian nuclear RNA N6-adenosine methylation in NATURE CHEMICAL BIOLOGY
  • 2011-10-16. N6-Methyladenosine in nuclear RNA is a major substrate of the obesity-associated FTO in NATURE CHEMICAL BIOLOGY
  • 2017-10-09. Essential role of METTL3-mediated m6A modification in glioma stem-like cells maintenance and radioresistance in ONCOGENE
  • 2018-07-21. Novel insights on m6A RNA methylation in tumorigenesis: a double-edged sword in MOLECULAR CANCER
  • 2013-01-25. WTAP regulates migration and invasion of cholangiocarcinoma cells in JOURNAL OF GASTROENTEROLOGY
  • 2018-02-23. Recognition of RNA N6-methyladenosine by IGF2BP proteins enhances mRNA stability and translation in NATURE CELL BIOLOGY
  • 2015-02-25. N6-methyladenosine-dependent RNA structural switches regulate RNA–protein interactions in NATURE
  • 2014-01-13. WTAP is a novel oncogenic protein in acute myeloid leukemia in LEUKEMIA
  • 1997-02-27. Conserved mechanisms of Ras regulation of evolutionary related transcription factors, Ets1 and Pointed P2 in ONCOGENE
  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1186/s12943-019-1053-8

    DOI

    http://dx.doi.org/10.1186/s12943-019-1053-8

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1120468774

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/31438961


    Indexing Status Check whether this publication has been indexed by Scopus and Web Of Science using the SN Indexing Status Tool
    Incoming Citations Browse incoming citations for this publication using opencitations.net

    JSON-LD is the canonical representation for SciGraph data.

    TIP: You can open this SciGraph record using an external JSON-LD service: JSON-LD Playground Google SDTT

    [
      {
        "@context": "https://springernature.github.io/scigraph/jsonld/sgcontext.json", 
        "about": [
          {
            "id": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/11", 
            "inDefinedTermSet": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/", 
            "name": "Medical and Health Sciences", 
            "type": "DefinedTerm"
          }, 
          {
            "id": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/1112", 
            "inDefinedTermSet": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/", 
            "name": "Oncology and Carcinogenesis", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Animals", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Carcinoma, Hepatocellular", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Cell Cycle", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Cell Cycle Proteins", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Cell Line, Tumor", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Cell Transformation, Neoplastic", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "DNA Methylation", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Disease Models, Animal", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "ELAV-Like Protein 1", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Epigenesis, Genetic", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Female", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Gene Silencing", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Humans", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Liver Neoplasms", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Male", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Methyltransferases", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Mice", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Models, Biological", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Neoplasm Staging", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Prognosis", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Proto-Oncogene Mas", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Proto-Oncogene Protein c-ets-1", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "RNA Splicing Factors", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Tumor Burden", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Xenograft Model Antitumor Assays", 
            "type": "DefinedTerm"
          }
        ], 
        "author": [
          {
            "affiliation": {
              "alternateName": "Key Laboratory of the Diagnosis and Treatment of Organ Transplantation, CAMS, Hangzhou, China", 
              "id": "http://www.grid.ac/institutes/grid.506261.6", 
              "name": [
                "Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China", 
                "Key Laboratory of Combined Multi-Organ Transplantation, Ministry of Public Health, Hangzhou, China", 
                "Key Laboratory of Organ Transplantation, Hangzhou, Zhejiang Province, China", 
                "Key Laboratory of the Diagnosis and Treatment of Organ Transplantation, CAMS, Hangzhou, China"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Chen", 
            "givenName": "Yunhao", 
            "id": "sg:person.015046712253.02", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.015046712253.02"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Key Laboratory of the Diagnosis and Treatment of Organ Transplantation, CAMS, Hangzhou, China", 
              "id": "http://www.grid.ac/institutes/grid.506261.6", 
              "name": [
                "Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China", 
                "Key Laboratory of Combined Multi-Organ Transplantation, Ministry of Public Health, Hangzhou, China", 
                "Key Laboratory of Organ Transplantation, Hangzhou, Zhejiang Province, China", 
                "Key Laboratory of the Diagnosis and Treatment of Organ Transplantation, CAMS, Hangzhou, China"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Peng", 
            "givenName": "Chuanhui", 
            "id": "sg:person.0736471050.59", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0736471050.59"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Key Laboratory of Organ Transplantation, Hangzhou, Zhejiang Province, China", 
              "id": "http://www.grid.ac/institutes/grid.452661.2", 
              "name": [
                "Key Laboratory of Combined Multi-Organ Transplantation, Ministry of Public Health, Hangzhou, China", 
                "Key Laboratory of Organ Transplantation, Hangzhou, Zhejiang Province, China"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Chen", 
            "givenName": "Junru", 
            "id": "sg:person.015013237071.14", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.015013237071.14"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Key Laboratory of Organ Transplantation, Hangzhou, Zhejiang Province, China", 
              "id": "http://www.grid.ac/institutes/grid.452661.2", 
              "name": [
                "Key Laboratory of Combined Multi-Organ Transplantation, Ministry of Public Health, Hangzhou, China", 
                "Key Laboratory of Organ Transplantation, Hangzhou, Zhejiang Province, China"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Chen", 
            "givenName": "Diyu", 
            "id": "sg:person.015133370034.91", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.015133370034.91"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Key Laboratory of Organ Transplantation, Hangzhou, Zhejiang Province, China", 
              "id": "http://www.grid.ac/institutes/grid.452661.2", 
              "name": [
                "Key Laboratory of Combined Multi-Organ Transplantation, Ministry of Public Health, Hangzhou, China", 
                "Key Laboratory of Organ Transplantation, Hangzhou, Zhejiang Province, China"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Yang", 
            "givenName": "Beng", 
            "id": "sg:person.012354763701.47", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.012354763701.47"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Key Laboratory of Organ Transplantation, Hangzhou, Zhejiang Province, China", 
              "id": "http://www.grid.ac/institutes/grid.452661.2", 
              "name": [
                "Key Laboratory of Combined Multi-Organ Transplantation, Ministry of Public Health, Hangzhou, China", 
                "Key Laboratory of Organ Transplantation, Hangzhou, Zhejiang Province, China"
              ], 
              "type": "Organization"
            }, 
            "familyName": "He", 
            "givenName": "Bin", 
            "id": "sg:person.01157531127.42", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01157531127.42"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Key Laboratory of Organ Transplantation, Hangzhou, Zhejiang Province, China", 
              "id": "http://www.grid.ac/institutes/grid.452661.2", 
              "name": [
                "Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China", 
                "Key Laboratory of Combined Multi-Organ Transplantation, Ministry of Public Health, Hangzhou, China", 
                "Key Laboratory of Organ Transplantation, Hangzhou, Zhejiang Province, China"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Hu", 
            "givenName": "Wendi", 
            "id": "sg:person.0707241735.24", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0707241735.24"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Key Laboratory of Organ Transplantation, Hangzhou, Zhejiang Province, China", 
              "id": "http://www.grid.ac/institutes/grid.452661.2", 
              "name": [
                "Key Laboratory of Combined Multi-Organ Transplantation, Ministry of Public Health, Hangzhou, China", 
                "Key Laboratory of Organ Transplantation, Hangzhou, Zhejiang Province, China"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Zhang", 
            "givenName": "Yanpeng", 
            "id": "sg:person.011454674027.44", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.011454674027.44"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Key Laboratory of Organ Transplantation, Hangzhou, Zhejiang Province, China", 
              "id": "http://www.grid.ac/institutes/grid.452661.2", 
              "name": [
                "Key Laboratory of Combined Multi-Organ Transplantation, Ministry of Public Health, Hangzhou, China", 
                "Key Laboratory of Organ Transplantation, Hangzhou, Zhejiang Province, China"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Liu", 
            "givenName": "Hua", 
            "id": "sg:person.07743634671.32", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.07743634671.32"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Key Laboratory of Organ Transplantation, Hangzhou, Zhejiang Province, China", 
              "id": "http://www.grid.ac/institutes/grid.452661.2", 
              "name": [
                "Key Laboratory of Combined Multi-Organ Transplantation, Ministry of Public Health, Hangzhou, China", 
                "Key Laboratory of Organ Transplantation, Hangzhou, Zhejiang Province, China"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Dai", 
            "givenName": "Longfei", 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Key Laboratory of the Diagnosis and Treatment of Organ Transplantation, CAMS, Hangzhou, China", 
              "id": "http://www.grid.ac/institutes/grid.506261.6", 
              "name": [
                "Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China", 
                "Key Laboratory of Combined Multi-Organ Transplantation, Ministry of Public Health, Hangzhou, China", 
                "Key Laboratory of Organ Transplantation, Hangzhou, Zhejiang Province, China", 
                "Key Laboratory of the Diagnosis and Treatment of Organ Transplantation, CAMS, Hangzhou, China"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Xie", 
            "givenName": "Haiyang", 
            "id": "sg:person.0657720126.04", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0657720126.04"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Key Laboratory of the Diagnosis and Treatment of Organ Transplantation, CAMS, Hangzhou, China", 
              "id": "http://www.grid.ac/institutes/grid.506261.6", 
              "name": [
                "Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China", 
                "Key Laboratory of Combined Multi-Organ Transplantation, Ministry of Public Health, Hangzhou, China", 
                "Key Laboratory of Organ Transplantation, Hangzhou, Zhejiang Province, China", 
                "Key Laboratory of the Diagnosis and Treatment of Organ Transplantation, CAMS, Hangzhou, China"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Zhou", 
            "givenName": "Lin", 
            "id": "sg:person.0753155421.39", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0753155421.39"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Key Laboratory of the Diagnosis and Treatment of Organ Transplantation, CAMS, Hangzhou, China", 
              "id": "http://www.grid.ac/institutes/grid.506261.6", 
              "name": [
                "Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China", 
                "Key Laboratory of the Diagnosis and Treatment of Organ Transplantation, CAMS, Hangzhou, China"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Wu", 
            "givenName": "Jian", 
            "id": "sg:person.014717003557.61", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.014717003557.61"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Key Laboratory of the Diagnosis and Treatment of Organ Transplantation, CAMS, Hangzhou, China", 
              "id": "http://www.grid.ac/institutes/grid.506261.6", 
              "name": [
                "Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China", 
                "Key Laboratory of Combined Multi-Organ Transplantation, Ministry of Public Health, Hangzhou, China", 
                "Key Laboratory of Organ Transplantation, Hangzhou, Zhejiang Province, China", 
                "Key Laboratory of the Diagnosis and Treatment of Organ Transplantation, CAMS, Hangzhou, China"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Zheng", 
            "givenName": "Shusen", 
            "id": "sg:person.0640501242.51", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0640501242.51"
            ], 
            "type": "Person"
          }
        ], 
        "citation": [
          {
            "id": "sg:pub.10.1038/nature14234", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1032360209", 
              "https://doi.org/10.1038/nature14234"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/nrm.2016.132", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1015710280", 
              "https://doi.org/10.1038/nrm.2016.132"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/s41556-018-0174-4", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1106199502", 
              "https://doi.org/10.1038/s41556-018-0174-4"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/nchembio.1432", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1027168512", 
              "https://doi.org/10.1038/nchembio.1432"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/nature20577", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1012535243", 
              "https://doi.org/10.1038/nature20577"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/s41421-018-0019-0", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1101201630", 
              "https://doi.org/10.1038/s41421-018-0019-0"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1186/s12964-018-0258-6", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1106331812", 
              "https://doi.org/10.1186/s12964-018-0258-6"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/nature12730", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1045996872", 
              "https://doi.org/10.1038/nature12730"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1007/s00535-013-0748-7", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1031044076", 
              "https://doi.org/10.1007/s00535-013-0748-7"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/leu.2014.16", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1019932266", 
              "https://doi.org/10.1038/leu.2014.16"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/ncb2902", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1049362451", 
              "https://doi.org/10.1038/ncb2902"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/onc.2017.351", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1092131998", 
              "https://doi.org/10.1038/onc.2017.351"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/nature18298", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1007258407", 
              "https://doi.org/10.1038/nature18298"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/cr.2017.15", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1053886237", 
              "https://doi.org/10.1038/cr.2017.15"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/cr.2014.3", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1027229236", 
              "https://doi.org/10.1038/cr.2014.3"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/sj.onc.1200914", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1044852920", 
              "https://doi.org/10.1038/sj.onc.1200914"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1186/s13046-018-0706-6", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1101228991", 
              "https://doi.org/10.1186/s13046-018-0706-6"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/nchembio.687", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1051364702", 
              "https://doi.org/10.1038/nchembio.687"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/s41556-018-0045-z", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1101059570", 
              "https://doi.org/10.1038/s41556-018-0045-z"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/nature19342", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1043394961", 
              "https://doi.org/10.1038/nature19342"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/nchembio.1654", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1011955349", 
              "https://doi.org/10.1038/nchembio.1654"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1186/s12943-018-0847-4", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1105762395", 
              "https://doi.org/10.1186/s12943-018-0847-4"
            ], 
            "type": "CreativeWork"
          }
        ], 
        "datePublished": "2019-08-22", 
        "datePublishedReg": "2019-08-22", 
        "description": "BackgroundN6-methyladenosine (m6A) methylation, a well-known modification with new epigenetic functions, has been reported to participate in the tumorigenesis of hepatocellular carcinoma (HCC), providing novel insights into the molecular pathogenesis of this disease. However, as the key component of m6A methylation, Wilms tumor 1-associated protein (WTAP) has not been well studied in HCC. Here we investigated the biological role and underlying mechanism of WTAP in liver cancer.MethodsWe determined the expression of WTAP and its correlation with clinicopathological features using tissue microarrays and the Cancer Genome Atlas (TCGA) dataset. And we clarified the effects of WTAP on HCC cells using cell proliferation assay, colony formation, Edu assay and subcutaneous xenograft experiments. We then applied RNA sequencing combined with gene expression omnibus (GEO) data to screen candidate targets of WTAP. Finally, we investigated the regulatory mechanism of WTAP in HCC by m6A dot blot assay, methylated RNA immunoprecipitation (MeRIP) assay, dual luciferase reporter assay, RNA immunoprecipitation (RIP) assay and Chromatin immunoprecipitation (ChIP) assay.ResultsWe demonstrated that WTAP was highly expressed in HCC which indicated the poor prognosis, and that WTAP expression served as an independent predictor of HCC survival. Functionally, WTAP promoted the proliferation capability and tumor growth of HCC cells in vitro and in vivo. Furthermore, ETS proto-oncogene 1 (ETS1) was identified as the downstream effector of WTAP. The m6A modification regulated by WTAP led to post-transcriptional suppression of ETS1, with the implication of Hu-Antigen R (HuR) as an RNA stabilizer. Then ETS1 was found to inhibit the progression of HCC and could rescue the phenotype induced by WTAP deficiency. Moreover, WTAP modulated the G2/M phase of HCC cells through a p21/p27-dependent pattern mediated by ETS1.ConclusionWe have identified that WTAP is significantly up-regulated in HCC and promotes liver cancer development. WTAP-guided m6A modification contributes to the progression of HCC via the HuR-ETS1-p21/p27 axis. Our study is the first to report that WTAP-mediated m6A methylation has a crucial role in HCC oncogenesis, and highlights WTAP as a potential therapeutic target of HCC treatment.", 
        "genre": "article", 
        "id": "sg:pub.10.1186/s12943-019-1053-8", 
        "isAccessibleForFree": true, 
        "isFundedItemOf": [
          {
            "id": "sg:grant.8366544", 
            "type": "MonetaryGrant"
          }, 
          {
            "id": "sg:grant.8880755", 
            "type": "MonetaryGrant"
          }
        ], 
        "isPartOf": [
          {
            "id": "sg:journal.1031030", 
            "issn": [
              "1476-4598"
            ], 
            "name": "Molecular Cancer", 
            "publisher": "Springer Nature", 
            "type": "Periodical"
          }, 
          {
            "issueNumber": "1", 
            "type": "PublicationIssue"
          }, 
          {
            "type": "PublicationVolume", 
            "volumeNumber": "18"
          }
        ], 
        "keywords": [
          "ETS proto-oncogene 1", 
          "RNA immunoprecipitation", 
          "m6A methylation", 
          "m6A modification", 
          "expression of WTAP", 
          "Gene Expression Omnibus data", 
          "post-transcriptional suppression", 
          "HCC cells", 
          "progression of HCC", 
          "epigenetic functions", 
          "dual-luciferase reporter", 
          "Hu antigen R", 
          "G2/M phase", 
          "Cancer Genome Atlas (TCGA) dataset", 
          "chromatin immunoprecipitation", 
          "epigenetic silencing", 
          "RNA sequencing", 
          "downstream effectors", 
          "hepatocellular carcinoma", 
          "p27 axis", 
          "regulatory mechanisms", 
          "biological role", 
          "WTAP expression", 
          "subcutaneous xenograft experiments", 
          "proto-oncogene 1", 
          "WTAP", 
          "Wilms tumor 1", 
          "luciferase reporter", 
          "novel insights", 
          "immunoprecipitation", 
          "methylation", 
          "M phase", 
          "colony formation", 
          "potential therapeutic target", 
          "candidate targets", 
          "xenograft experiments", 
          "Atlas dataset", 
          "cell proliferation", 
          "cancer development", 
          "dot blot assay", 
          "proliferation capability", 
          "blot assays", 
          "molecular pathogenesis", 
          "liver cancer development", 
          "RNA stabilizer", 
          "tumor 1", 
          "therapeutic target", 
          "cells", 
          "tumor growth", 
          "crucial role", 
          "expression", 
          "underlying mechanism", 
          "HCC oncogenesis", 
          "independent predictors", 
          "clinicopathological features", 
          "poor prognosis", 
          "liver cancer", 
          "HCC survival", 
          "tissue microarray", 
          "HCC treatment", 
          "silencing", 
          "key component", 
          "sequencing", 
          "reporter", 
          "oncogenesis", 
          "protein", 
          "effectors", 
          "microarray", 
          "tumorigenesis", 
          "target", 
          "phenotype", 
          "progression", 
          "carcinoma", 
          "modification", 
          "mechanism", 
          "EdU", 
          "role", 
          "proliferation", 
          "vitro", 
          "assays", 
          "vivo", 
          "growth", 
          "prognosis", 
          "insights", 
          "pathogenesis", 
          "cancer", 
          "MethodsWe", 
          "disease", 
          "ResultsWe", 
          "survival", 
          "suppression", 
          "treatment", 
          "deficiency", 
          "predictors", 
          "function", 
          "patterns", 
          "formation", 
          "development", 
          "components", 
          "highlights", 
          "axis", 
          "study", 
          "correlation", 
          "experiments", 
          "effect", 
          "dataset", 
          "implications", 
          "data", 
          "features", 
          "phase", 
          "stabilizer", 
          "capability"
        ], 
        "name": "WTAP facilitates progression of hepatocellular carcinoma via m6A-HuR-dependent epigenetic silencing of ETS1", 
        "pagination": "127", 
        "productId": [
          {
            "name": "dimensions_id", 
            "type": "PropertyValue", 
            "value": [
              "pub.1120468774"
            ]
          }, 
          {
            "name": "doi", 
            "type": "PropertyValue", 
            "value": [
              "10.1186/s12943-019-1053-8"
            ]
          }, 
          {
            "name": "pubmed_id", 
            "type": "PropertyValue", 
            "value": [
              "31438961"
            ]
          }
        ], 
        "sameAs": [
          "https://doi.org/10.1186/s12943-019-1053-8", 
          "https://app.dimensions.ai/details/publication/pub.1120468774"
        ], 
        "sdDataset": "articles", 
        "sdDatePublished": "2022-10-01T06:46", 
        "sdLicense": "https://scigraph.springernature.com/explorer/license/", 
        "sdPublisher": {
          "name": "Springer Nature - SN SciGraph project", 
          "type": "Organization"
        }, 
        "sdSource": "s3://com-springernature-scigraph/baseset/20221001/entities/gbq_results/article/article_834.jsonl", 
        "type": "ScholarlyArticle", 
        "url": "https://doi.org/10.1186/s12943-019-1053-8"
      }
    ]
     

    Download the RDF metadata as:  json-ld nt turtle xml License info

    HOW TO GET THIS DATA PROGRAMMATICALLY:

    JSON-LD is a popular format for linked data which is fully compatible with JSON.

    curl -H 'Accept: application/ld+json' 'https://scigraph.springernature.com/pub.10.1186/s12943-019-1053-8'

    N-Triples is a line-based linked data format ideal for batch operations.

    curl -H 'Accept: application/n-triples' 'https://scigraph.springernature.com/pub.10.1186/s12943-019-1053-8'

    Turtle is a human-readable linked data format.

    curl -H 'Accept: text/turtle' 'https://scigraph.springernature.com/pub.10.1186/s12943-019-1053-8'

    RDF/XML is a standard XML format for linked data.

    curl -H 'Accept: application/rdf+xml' 'https://scigraph.springernature.com/pub.10.1186/s12943-019-1053-8'


     

    This table displays all metadata directly associated to this object as RDF triples.

    462 TRIPLES      21 PREDICATES      184 URIs      154 LITERALS      32 BLANK NODES

    Subject Predicate Object
    1 sg:pub.10.1186/s12943-019-1053-8 schema:about N153c66e452894f4bb06856d5eed205a5
    2 N165781e9e10548e88cf789a373c3f444
    3 N1a915b68bb4f4c0290b7386645543631
    4 N27054a9ee0eb42bab5dfdb4e01dce0a9
    5 N2ae8fa061a4f48b9bab75c4c557b487a
    6 N2c1dad3fe8f14281b5694727df8754c1
    7 N41347a6927ee49a08ef5623db1c0c789
    8 N5b868bdcc40f46b1a4382bee1e0dba0f
    9 N62feb492bb544f988404b0d3c7bf786d
    10 N8ce660f8393b4c3ea8d2197d53c3aa2c
    11 N8d70402232f94e9fb259fb43dd70258d
    12 N95c8fc4c03a44919be5174e5e6d8e764
    13 N9643351a333246f596a398458718d3ed
    14 Na951f1a2252f4e6c83a45f61b6dbc869
    15 Nb1ad25f7d8c1446dbc591bc748b7de56
    16 Nb5c6c604beaa49ca9a7db73302e48479
    17 Nb61568d73e7d45e3b0e2dbac05cfb474
    18 Nb720cd2d2b154e2da7b28b18848c9bd5
    19 Nbfd063cb7e3c4208bd482842531e7ce2
    20 Ncebf2149249743ef9d184d82d23c8ff0
    21 Nd39beaef444f4ad5a1d37e6dbe1ff835
    22 Nd7eb1b3109c94ea59629c1924db6b412
    23 Neb5e81870e844a3799228c6972afa00d
    24 Nee7313cda2ce4fb59f1c2c9aab03b0a2
    25 Nfbd30014ad8a4cbebe0d25b432b40f17
    26 anzsrc-for:11
    27 anzsrc-for:1112
    28 schema:author N5012090d58a34c239c0198ddc4b6c5ff
    29 schema:citation sg:pub.10.1007/s00535-013-0748-7
    30 sg:pub.10.1038/cr.2014.3
    31 sg:pub.10.1038/cr.2017.15
    32 sg:pub.10.1038/leu.2014.16
    33 sg:pub.10.1038/nature12730
    34 sg:pub.10.1038/nature14234
    35 sg:pub.10.1038/nature18298
    36 sg:pub.10.1038/nature19342
    37 sg:pub.10.1038/nature20577
    38 sg:pub.10.1038/ncb2902
    39 sg:pub.10.1038/nchembio.1432
    40 sg:pub.10.1038/nchembio.1654
    41 sg:pub.10.1038/nchembio.687
    42 sg:pub.10.1038/nrm.2016.132
    43 sg:pub.10.1038/onc.2017.351
    44 sg:pub.10.1038/s41421-018-0019-0
    45 sg:pub.10.1038/s41556-018-0045-z
    46 sg:pub.10.1038/s41556-018-0174-4
    47 sg:pub.10.1038/sj.onc.1200914
    48 sg:pub.10.1186/s12943-018-0847-4
    49 sg:pub.10.1186/s12964-018-0258-6
    50 sg:pub.10.1186/s13046-018-0706-6
    51 schema:datePublished 2019-08-22
    52 schema:datePublishedReg 2019-08-22
    53 schema:description BackgroundN6-methyladenosine (m6A) methylation, a well-known modification with new epigenetic functions, has been reported to participate in the tumorigenesis of hepatocellular carcinoma (HCC), providing novel insights into the molecular pathogenesis of this disease. However, as the key component of m6A methylation, Wilms tumor 1-associated protein (WTAP) has not been well studied in HCC. Here we investigated the biological role and underlying mechanism of WTAP in liver cancer.MethodsWe determined the expression of WTAP and its correlation with clinicopathological features using tissue microarrays and the Cancer Genome Atlas (TCGA) dataset. And we clarified the effects of WTAP on HCC cells using cell proliferation assay, colony formation, Edu assay and subcutaneous xenograft experiments. We then applied RNA sequencing combined with gene expression omnibus (GEO) data to screen candidate targets of WTAP. Finally, we investigated the regulatory mechanism of WTAP in HCC by m6A dot blot assay, methylated RNA immunoprecipitation (MeRIP) assay, dual luciferase reporter assay, RNA immunoprecipitation (RIP) assay and Chromatin immunoprecipitation (ChIP) assay.ResultsWe demonstrated that WTAP was highly expressed in HCC which indicated the poor prognosis, and that WTAP expression served as an independent predictor of HCC survival. Functionally, WTAP promoted the proliferation capability and tumor growth of HCC cells in vitro and in vivo. Furthermore, ETS proto-oncogene 1 (ETS1) was identified as the downstream effector of WTAP. The m6A modification regulated by WTAP led to post-transcriptional suppression of ETS1, with the implication of Hu-Antigen R (HuR) as an RNA stabilizer. Then ETS1 was found to inhibit the progression of HCC and could rescue the phenotype induced by WTAP deficiency. Moreover, WTAP modulated the G2/M phase of HCC cells through a p21/p27-dependent pattern mediated by ETS1.ConclusionWe have identified that WTAP is significantly up-regulated in HCC and promotes liver cancer development. WTAP-guided m6A modification contributes to the progression of HCC via the HuR-ETS1-p21/p27 axis. Our study is the first to report that WTAP-mediated m6A methylation has a crucial role in HCC oncogenesis, and highlights WTAP as a potential therapeutic target of HCC treatment.
    54 schema:genre article
    55 schema:isAccessibleForFree true
    56 schema:isPartOf N855230566ce84f2b9a81626b3eebd069
    57 Nb06f4d1f0cd84e299d4a5af9eb99d6cf
    58 sg:journal.1031030
    59 schema:keywords Atlas dataset
    60 Cancer Genome Atlas (TCGA) dataset
    61 ETS proto-oncogene 1
    62 EdU
    63 G2/M phase
    64 Gene Expression Omnibus data
    65 HCC cells
    66 HCC oncogenesis
    67 HCC survival
    68 HCC treatment
    69 Hu antigen R
    70 M phase
    71 MethodsWe
    72 RNA immunoprecipitation
    73 RNA sequencing
    74 RNA stabilizer
    75 ResultsWe
    76 WTAP
    77 WTAP expression
    78 Wilms tumor 1
    79 assays
    80 axis
    81 biological role
    82 blot assays
    83 cancer
    84 cancer development
    85 candidate targets
    86 capability
    87 carcinoma
    88 cell proliferation
    89 cells
    90 chromatin immunoprecipitation
    91 clinicopathological features
    92 colony formation
    93 components
    94 correlation
    95 crucial role
    96 data
    97 dataset
    98 deficiency
    99 development
    100 disease
    101 dot blot assay
    102 downstream effectors
    103 dual-luciferase reporter
    104 effect
    105 effectors
    106 epigenetic functions
    107 epigenetic silencing
    108 experiments
    109 expression
    110 expression of WTAP
    111 features
    112 formation
    113 function
    114 growth
    115 hepatocellular carcinoma
    116 highlights
    117 immunoprecipitation
    118 implications
    119 independent predictors
    120 insights
    121 key component
    122 liver cancer
    123 liver cancer development
    124 luciferase reporter
    125 m6A methylation
    126 m6A modification
    127 mechanism
    128 methylation
    129 microarray
    130 modification
    131 molecular pathogenesis
    132 novel insights
    133 oncogenesis
    134 p27 axis
    135 pathogenesis
    136 patterns
    137 phase
    138 phenotype
    139 poor prognosis
    140 post-transcriptional suppression
    141 potential therapeutic target
    142 predictors
    143 prognosis
    144 progression
    145 progression of HCC
    146 proliferation
    147 proliferation capability
    148 protein
    149 proto-oncogene 1
    150 regulatory mechanisms
    151 reporter
    152 role
    153 sequencing
    154 silencing
    155 stabilizer
    156 study
    157 subcutaneous xenograft experiments
    158 suppression
    159 survival
    160 target
    161 therapeutic target
    162 tissue microarray
    163 treatment
    164 tumor 1
    165 tumor growth
    166 tumorigenesis
    167 underlying mechanism
    168 vitro
    169 vivo
    170 xenograft experiments
    171 schema:name WTAP facilitates progression of hepatocellular carcinoma via m6A-HuR-dependent epigenetic silencing of ETS1
    172 schema:pagination 127
    173 schema:productId N5b4df72db016441b803682c50426dffb
    174 Na92fda92ddd2499aab5abc862b836db8
    175 Nede3ce7b4e264fd0b75618c9e60b33fe
    176 schema:sameAs https://app.dimensions.ai/details/publication/pub.1120468774
    177 https://doi.org/10.1186/s12943-019-1053-8
    178 schema:sdDatePublished 2022-10-01T06:46
    179 schema:sdLicense https://scigraph.springernature.com/explorer/license/
    180 schema:sdPublisher Nf5f599abf88a4f47b346c1b3366cfaa0
    181 schema:url https://doi.org/10.1186/s12943-019-1053-8
    182 sgo:license sg:explorer/license/
    183 sgo:sdDataset articles
    184 rdf:type schema:ScholarlyArticle
    185 N02dc20ea68694cea915f29acca396707 schema:affiliation grid-institutes:grid.452661.2
    186 schema:familyName Dai
    187 schema:givenName Longfei
    188 rdf:type schema:Person
    189 N04934d8fb5604e3d894179cb0f6e76ae rdf:first N02dc20ea68694cea915f29acca396707
    190 rdf:rest Ne4312313ebd64054a01d7e90ac8aadee
    191 N0ce9d8c53fd841a991a090445721e4cf rdf:first sg:person.011454674027.44
    192 rdf:rest N2607771374e34baa965b89586a6ef7d1
    193 N153c66e452894f4bb06856d5eed205a5 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    194 schema:name Cell Cycle
    195 rdf:type schema:DefinedTerm
    196 N165781e9e10548e88cf789a373c3f444 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    197 schema:name Disease Models, Animal
    198 rdf:type schema:DefinedTerm
    199 N1a915b68bb4f4c0290b7386645543631 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    200 schema:name ELAV-Like Protein 1
    201 rdf:type schema:DefinedTerm
    202 N2607771374e34baa965b89586a6ef7d1 rdf:first sg:person.07743634671.32
    203 rdf:rest N04934d8fb5604e3d894179cb0f6e76ae
    204 N27054a9ee0eb42bab5dfdb4e01dce0a9 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    205 schema:name Humans
    206 rdf:type schema:DefinedTerm
    207 N2ae8fa061a4f48b9bab75c4c557b487a schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    208 schema:name Models, Biological
    209 rdf:type schema:DefinedTerm
    210 N2c1dad3fe8f14281b5694727df8754c1 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    211 schema:name Prognosis
    212 rdf:type schema:DefinedTerm
    213 N368fcb0a62094f89a1540d171ea4debe rdf:first sg:person.01157531127.42
    214 rdf:rest Naaf1c0cb96224cba8fc54606cab358fc
    215 N41347a6927ee49a08ef5623db1c0c789 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    216 schema:name Epigenesis, Genetic
    217 rdf:type schema:DefinedTerm
    218 N5012090d58a34c239c0198ddc4b6c5ff rdf:first sg:person.015046712253.02
    219 rdf:rest Nc56c30f6e3304fc291e21cef38abd08c
    220 N53fd5350d00b4f0bbfeecdbb6d91c967 rdf:first sg:person.012354763701.47
    221 rdf:rest N368fcb0a62094f89a1540d171ea4debe
    222 N5b4df72db016441b803682c50426dffb schema:name doi
    223 schema:value 10.1186/s12943-019-1053-8
    224 rdf:type schema:PropertyValue
    225 N5b868bdcc40f46b1a4382bee1e0dba0f schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    226 schema:name Methyltransferases
    227 rdf:type schema:DefinedTerm
    228 N5d7bcac030eb400ba74a44a0684e47f3 rdf:first sg:person.015133370034.91
    229 rdf:rest N53fd5350d00b4f0bbfeecdbb6d91c967
    230 N6084ddd0e36e4f759be7bdd92a29c683 rdf:first sg:person.0753155421.39
    231 rdf:rest Nb88b28413dec4886b5773ee0307c29e5
    232 N62feb492bb544f988404b0d3c7bf786d schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    233 schema:name Carcinoma, Hepatocellular
    234 rdf:type schema:DefinedTerm
    235 N855230566ce84f2b9a81626b3eebd069 schema:volumeNumber 18
    236 rdf:type schema:PublicationVolume
    237 N8ce660f8393b4c3ea8d2197d53c3aa2c schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    238 schema:name DNA Methylation
    239 rdf:type schema:DefinedTerm
    240 N8d70402232f94e9fb259fb43dd70258d schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    241 schema:name Cell Cycle Proteins
    242 rdf:type schema:DefinedTerm
    243 N95c8fc4c03a44919be5174e5e6d8e764 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    244 schema:name Animals
    245 rdf:type schema:DefinedTerm
    246 N9643351a333246f596a398458718d3ed schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    247 schema:name Female
    248 rdf:type schema:DefinedTerm
    249 Na92fda92ddd2499aab5abc862b836db8 schema:name pubmed_id
    250 schema:value 31438961
    251 rdf:type schema:PropertyValue
    252 Na951f1a2252f4e6c83a45f61b6dbc869 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    253 schema:name Liver Neoplasms
    254 rdf:type schema:DefinedTerm
    255 Naaf1c0cb96224cba8fc54606cab358fc rdf:first sg:person.0707241735.24
    256 rdf:rest N0ce9d8c53fd841a991a090445721e4cf
    257 Nb06f4d1f0cd84e299d4a5af9eb99d6cf schema:issueNumber 1
    258 rdf:type schema:PublicationIssue
    259 Nb0d2ffd8562f471faf5a791fc1c8ad49 rdf:first sg:person.0640501242.51
    260 rdf:rest rdf:nil
    261 Nb1ad25f7d8c1446dbc591bc748b7de56 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    262 schema:name Male
    263 rdf:type schema:DefinedTerm
    264 Nb5c6c604beaa49ca9a7db73302e48479 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    265 schema:name Cell Transformation, Neoplastic
    266 rdf:type schema:DefinedTerm
    267 Nb61568d73e7d45e3b0e2dbac05cfb474 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    268 schema:name Neoplasm Staging
    269 rdf:type schema:DefinedTerm
    270 Nb720cd2d2b154e2da7b28b18848c9bd5 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    271 schema:name Proto-Oncogene Protein c-ets-1
    272 rdf:type schema:DefinedTerm
    273 Nb88b28413dec4886b5773ee0307c29e5 rdf:first sg:person.014717003557.61
    274 rdf:rest Nb0d2ffd8562f471faf5a791fc1c8ad49
    275 Nba7ae4cb38e44ef490ba9d9619c27a1e rdf:first sg:person.015013237071.14
    276 rdf:rest N5d7bcac030eb400ba74a44a0684e47f3
    277 Nbfd063cb7e3c4208bd482842531e7ce2 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    278 schema:name Xenograft Model Antitumor Assays
    279 rdf:type schema:DefinedTerm
    280 Nc56c30f6e3304fc291e21cef38abd08c rdf:first sg:person.0736471050.59
    281 rdf:rest Nba7ae4cb38e44ef490ba9d9619c27a1e
    282 Ncebf2149249743ef9d184d82d23c8ff0 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    283 schema:name Gene Silencing
    284 rdf:type schema:DefinedTerm
    285 Nd39beaef444f4ad5a1d37e6dbe1ff835 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    286 schema:name RNA Splicing Factors
    287 rdf:type schema:DefinedTerm
    288 Nd7eb1b3109c94ea59629c1924db6b412 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    289 schema:name Cell Line, Tumor
    290 rdf:type schema:DefinedTerm
    291 Ne4312313ebd64054a01d7e90ac8aadee rdf:first sg:person.0657720126.04
    292 rdf:rest N6084ddd0e36e4f759be7bdd92a29c683
    293 Neb5e81870e844a3799228c6972afa00d schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    294 schema:name Proto-Oncogene Mas
    295 rdf:type schema:DefinedTerm
    296 Nede3ce7b4e264fd0b75618c9e60b33fe schema:name dimensions_id
    297 schema:value pub.1120468774
    298 rdf:type schema:PropertyValue
    299 Nee7313cda2ce4fb59f1c2c9aab03b0a2 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    300 schema:name Tumor Burden
    301 rdf:type schema:DefinedTerm
    302 Nf5f599abf88a4f47b346c1b3366cfaa0 schema:name Springer Nature - SN SciGraph project
    303 rdf:type schema:Organization
    304 Nfbd30014ad8a4cbebe0d25b432b40f17 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    305 schema:name Mice
    306 rdf:type schema:DefinedTerm
    307 anzsrc-for:11 schema:inDefinedTermSet anzsrc-for:
    308 schema:name Medical and Health Sciences
    309 rdf:type schema:DefinedTerm
    310 anzsrc-for:1112 schema:inDefinedTermSet anzsrc-for:
    311 schema:name Oncology and Carcinogenesis
    312 rdf:type schema:DefinedTerm
    313 sg:grant.8366544 http://pending.schema.org/fundedItem sg:pub.10.1186/s12943-019-1053-8
    314 rdf:type schema:MonetaryGrant
    315 sg:grant.8880755 http://pending.schema.org/fundedItem sg:pub.10.1186/s12943-019-1053-8
    316 rdf:type schema:MonetaryGrant
    317 sg:journal.1031030 schema:issn 1476-4598
    318 schema:name Molecular Cancer
    319 schema:publisher Springer Nature
    320 rdf:type schema:Periodical
    321 sg:person.011454674027.44 schema:affiliation grid-institutes:grid.452661.2
    322 schema:familyName Zhang
    323 schema:givenName Yanpeng
    324 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.011454674027.44
    325 rdf:type schema:Person
    326 sg:person.01157531127.42 schema:affiliation grid-institutes:grid.452661.2
    327 schema:familyName He
    328 schema:givenName Bin
    329 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01157531127.42
    330 rdf:type schema:Person
    331 sg:person.012354763701.47 schema:affiliation grid-institutes:grid.452661.2
    332 schema:familyName Yang
    333 schema:givenName Beng
    334 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.012354763701.47
    335 rdf:type schema:Person
    336 sg:person.014717003557.61 schema:affiliation grid-institutes:grid.506261.6
    337 schema:familyName Wu
    338 schema:givenName Jian
    339 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.014717003557.61
    340 rdf:type schema:Person
    341 sg:person.015013237071.14 schema:affiliation grid-institutes:grid.452661.2
    342 schema:familyName Chen
    343 schema:givenName Junru
    344 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.015013237071.14
    345 rdf:type schema:Person
    346 sg:person.015046712253.02 schema:affiliation grid-institutes:grid.506261.6
    347 schema:familyName Chen
    348 schema:givenName Yunhao
    349 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.015046712253.02
    350 rdf:type schema:Person
    351 sg:person.015133370034.91 schema:affiliation grid-institutes:grid.452661.2
    352 schema:familyName Chen
    353 schema:givenName Diyu
    354 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.015133370034.91
    355 rdf:type schema:Person
    356 sg:person.0640501242.51 schema:affiliation grid-institutes:grid.506261.6
    357 schema:familyName Zheng
    358 schema:givenName Shusen
    359 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0640501242.51
    360 rdf:type schema:Person
    361 sg:person.0657720126.04 schema:affiliation grid-institutes:grid.506261.6
    362 schema:familyName Xie
    363 schema:givenName Haiyang
    364 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0657720126.04
    365 rdf:type schema:Person
    366 sg:person.0707241735.24 schema:affiliation grid-institutes:grid.452661.2
    367 schema:familyName Hu
    368 schema:givenName Wendi
    369 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0707241735.24
    370 rdf:type schema:Person
    371 sg:person.0736471050.59 schema:affiliation grid-institutes:grid.506261.6
    372 schema:familyName Peng
    373 schema:givenName Chuanhui
    374 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0736471050.59
    375 rdf:type schema:Person
    376 sg:person.0753155421.39 schema:affiliation grid-institutes:grid.506261.6
    377 schema:familyName Zhou
    378 schema:givenName Lin
    379 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0753155421.39
    380 rdf:type schema:Person
    381 sg:person.07743634671.32 schema:affiliation grid-institutes:grid.452661.2
    382 schema:familyName Liu
    383 schema:givenName Hua
    384 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.07743634671.32
    385 rdf:type schema:Person
    386 sg:pub.10.1007/s00535-013-0748-7 schema:sameAs https://app.dimensions.ai/details/publication/pub.1031044076
    387 https://doi.org/10.1007/s00535-013-0748-7
    388 rdf:type schema:CreativeWork
    389 sg:pub.10.1038/cr.2014.3 schema:sameAs https://app.dimensions.ai/details/publication/pub.1027229236
    390 https://doi.org/10.1038/cr.2014.3
    391 rdf:type schema:CreativeWork
    392 sg:pub.10.1038/cr.2017.15 schema:sameAs https://app.dimensions.ai/details/publication/pub.1053886237
    393 https://doi.org/10.1038/cr.2017.15
    394 rdf:type schema:CreativeWork
    395 sg:pub.10.1038/leu.2014.16 schema:sameAs https://app.dimensions.ai/details/publication/pub.1019932266
    396 https://doi.org/10.1038/leu.2014.16
    397 rdf:type schema:CreativeWork
    398 sg:pub.10.1038/nature12730 schema:sameAs https://app.dimensions.ai/details/publication/pub.1045996872
    399 https://doi.org/10.1038/nature12730
    400 rdf:type schema:CreativeWork
    401 sg:pub.10.1038/nature14234 schema:sameAs https://app.dimensions.ai/details/publication/pub.1032360209
    402 https://doi.org/10.1038/nature14234
    403 rdf:type schema:CreativeWork
    404 sg:pub.10.1038/nature18298 schema:sameAs https://app.dimensions.ai/details/publication/pub.1007258407
    405 https://doi.org/10.1038/nature18298
    406 rdf:type schema:CreativeWork
    407 sg:pub.10.1038/nature19342 schema:sameAs https://app.dimensions.ai/details/publication/pub.1043394961
    408 https://doi.org/10.1038/nature19342
    409 rdf:type schema:CreativeWork
    410 sg:pub.10.1038/nature20577 schema:sameAs https://app.dimensions.ai/details/publication/pub.1012535243
    411 https://doi.org/10.1038/nature20577
    412 rdf:type schema:CreativeWork
    413 sg:pub.10.1038/ncb2902 schema:sameAs https://app.dimensions.ai/details/publication/pub.1049362451
    414 https://doi.org/10.1038/ncb2902
    415 rdf:type schema:CreativeWork
    416 sg:pub.10.1038/nchembio.1432 schema:sameAs https://app.dimensions.ai/details/publication/pub.1027168512
    417 https://doi.org/10.1038/nchembio.1432
    418 rdf:type schema:CreativeWork
    419 sg:pub.10.1038/nchembio.1654 schema:sameAs https://app.dimensions.ai/details/publication/pub.1011955349
    420 https://doi.org/10.1038/nchembio.1654
    421 rdf:type schema:CreativeWork
    422 sg:pub.10.1038/nchembio.687 schema:sameAs https://app.dimensions.ai/details/publication/pub.1051364702
    423 https://doi.org/10.1038/nchembio.687
    424 rdf:type schema:CreativeWork
    425 sg:pub.10.1038/nrm.2016.132 schema:sameAs https://app.dimensions.ai/details/publication/pub.1015710280
    426 https://doi.org/10.1038/nrm.2016.132
    427 rdf:type schema:CreativeWork
    428 sg:pub.10.1038/onc.2017.351 schema:sameAs https://app.dimensions.ai/details/publication/pub.1092131998
    429 https://doi.org/10.1038/onc.2017.351
    430 rdf:type schema:CreativeWork
    431 sg:pub.10.1038/s41421-018-0019-0 schema:sameAs https://app.dimensions.ai/details/publication/pub.1101201630
    432 https://doi.org/10.1038/s41421-018-0019-0
    433 rdf:type schema:CreativeWork
    434 sg:pub.10.1038/s41556-018-0045-z schema:sameAs https://app.dimensions.ai/details/publication/pub.1101059570
    435 https://doi.org/10.1038/s41556-018-0045-z
    436 rdf:type schema:CreativeWork
    437 sg:pub.10.1038/s41556-018-0174-4 schema:sameAs https://app.dimensions.ai/details/publication/pub.1106199502
    438 https://doi.org/10.1038/s41556-018-0174-4
    439 rdf:type schema:CreativeWork
    440 sg:pub.10.1038/sj.onc.1200914 schema:sameAs https://app.dimensions.ai/details/publication/pub.1044852920
    441 https://doi.org/10.1038/sj.onc.1200914
    442 rdf:type schema:CreativeWork
    443 sg:pub.10.1186/s12943-018-0847-4 schema:sameAs https://app.dimensions.ai/details/publication/pub.1105762395
    444 https://doi.org/10.1186/s12943-018-0847-4
    445 rdf:type schema:CreativeWork
    446 sg:pub.10.1186/s12964-018-0258-6 schema:sameAs https://app.dimensions.ai/details/publication/pub.1106331812
    447 https://doi.org/10.1186/s12964-018-0258-6
    448 rdf:type schema:CreativeWork
    449 sg:pub.10.1186/s13046-018-0706-6 schema:sameAs https://app.dimensions.ai/details/publication/pub.1101228991
    450 https://doi.org/10.1186/s13046-018-0706-6
    451 rdf:type schema:CreativeWork
    452 grid-institutes:grid.452661.2 schema:alternateName Key Laboratory of Organ Transplantation, Hangzhou, Zhejiang Province, China
    453 schema:name Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
    454 Key Laboratory of Combined Multi-Organ Transplantation, Ministry of Public Health, Hangzhou, China
    455 Key Laboratory of Organ Transplantation, Hangzhou, Zhejiang Province, China
    456 rdf:type schema:Organization
    457 grid-institutes:grid.506261.6 schema:alternateName Key Laboratory of the Diagnosis and Treatment of Organ Transplantation, CAMS, Hangzhou, China
    458 schema:name Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
    459 Key Laboratory of Combined Multi-Organ Transplantation, Ministry of Public Health, Hangzhou, China
    460 Key Laboratory of Organ Transplantation, Hangzhou, Zhejiang Province, China
    461 Key Laboratory of the Diagnosis and Treatment of Organ Transplantation, CAMS, Hangzhou, China
    462 rdf:type schema:Organization
     




    Preview window. Press ESC to close (or click here)


    ...