Genome-wide CRISPR screen reveals SGOL1 as a druggable target of sorafenib-treated hepatocellular carcinoma View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2018-02-21

AUTHORS

Weijian Sun, Bin He, Beng Yang, Wendi Hu, Shaobing Cheng, Heng Xiao, Zhengjie Yang, Xiaoyu Wen, Lin Zhou, Haiyang Xie, Xian Shen, Jian Wu, Shusen Zheng

ABSTRACT

The genome-wide clustered regularly interspaced short palindromic repeats (CRISPR) screen is a powerful tool used to identify therapeutic targets that can be harnessed for cancer treatment. This study aimed to assess the efficacy of genome-wide CRISPR screening to identify druggable genes associated with sorafenib-treated hepatocellular carcinoma (HCC). A genome-scale CRISPR knockout (GeCKO v2) library containing 123,411 single guide RNAs (sgRNAs) was used to identify loss-of-function mutations conferring sorafenib resistance upon HCC cells. Resistance gene screens identified SGOL1 as an indicator of prognosis of patients treated with sorafenib. Of the 19,050 genes tested, the knockout screen identified inhibition of SGOL1 expression as the most-effective genetic suppressor of sorafenib activity. Analysis of the survival of 210 patients with HCC after hepatic resection revealed that high SGOL1 expression shortened overall survival (P = 0.021). Further, matched pairs analysis of the TCGA database revealed that SGOL1 is differentially expressed. When we used a lentivirus Cas9 vector to determine the effect of targeting SGOL1 with a specific sgRNA in HCC cells, we found that SGOL1 expression was efficiently inhibited and that loss of SGOL1 was associated with sorafenib resistance. Further, loss of SGOL1 from HCC cell decreased the cytotoxicity of sorafenib in vivo. We conclude that the CRISPR screen is a powerful tool for therapeutic target analysis of sorafenib treatment and that SGOL1 serves as a druggable target for HCC treated with sorafenib and an indicator of prognosis. More... »

PAGES

734-744

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/s41374-018-0027-6

DOI

http://dx.doi.org/10.1038/s41374-018-0027-6

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1101141666

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/29467456


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": "Antineoplastic Agents", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Carcinoma, Hepatocellular", 
        "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": "Clustered Regularly Interspaced Short Palindromic Repeats", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Drug Resistance, Neoplasm", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Gene Knockdown Techniques", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Genome-Wide Association Study", 
        "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": "Mice", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Mice, Inbred BALB C", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Prognosis", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Sorafenib", 
        "type": "DefinedTerm"
      }
    ], 
    "author": [
      {
        "affiliation": {
          "alternateName": "Key Laboratory of Organ Transplantation, 310003, Hangzhou, Zhejiang Province, China", 
          "id": "http://www.grid.ac/institutes/grid.452661.2", 
          "name": [
            "Department of Surgery, The Second Affiliated Hospital and Yuying Children\u2019s Hospital of Wenzhou Medical University, 325027, Wenzhou, China", 
            "Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, 310003, Hangzhou, China", 
            "Key Laboratory of Combined Multi-organ Transplantation, Ministry of Public Health, 310003, Hangzhou, Zhejiang Province, China", 
            "Key Laboratory of Organ Transplantation, 310003, Hangzhou, Zhejiang Province, China"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Sun", 
        "givenName": "Weijian", 
        "id": "sg:person.014250455551.61", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.014250455551.61"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Key Laboratory of Organ Transplantation, 310003, 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, 310003, Hangzhou, China", 
            "Key Laboratory of Combined Multi-organ Transplantation, Ministry of Public Health, 310003, Hangzhou, Zhejiang Province, China", 
            "Key Laboratory of Organ Transplantation, 310003, 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, 310003, 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, 310003, Hangzhou, China", 
            "Key Laboratory of Combined Multi-organ Transplantation, Ministry of Public Health, 310003, Hangzhou, Zhejiang Province, China", 
            "Key Laboratory of Organ Transplantation, 310003, 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, 310003, 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, 310003, Hangzhou, China", 
            "Key Laboratory of Combined Multi-organ Transplantation, Ministry of Public Health, 310003, Hangzhou, Zhejiang Province, China", 
            "Key Laboratory of Organ Transplantation, 310003, 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, 310003, 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, 310003, Hangzhou, China", 
            "Key Laboratory of Combined Multi-organ Transplantation, Ministry of Public Health, 310003, Hangzhou, Zhejiang Province, China", 
            "Key Laboratory of Organ Transplantation, 310003, Hangzhou, Zhejiang Province, China"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Cheng", 
        "givenName": "Shaobing", 
        "id": "sg:person.01152647226.17", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01152647226.17"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Key Laboratory of Organ Transplantation, 310003, 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, 310003, Hangzhou, China", 
            "Key Laboratory of Combined Multi-organ Transplantation, Ministry of Public Health, 310003, Hangzhou, Zhejiang Province, China", 
            "Key Laboratory of Organ Transplantation, 310003, Hangzhou, Zhejiang Province, China"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Xiao", 
        "givenName": "Heng", 
        "id": "sg:person.01104534026.18", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01104534026.18"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Key Laboratory of Organ Transplantation, 310003, 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, 310003, Hangzhou, China", 
            "Key Laboratory of Combined Multi-organ Transplantation, Ministry of Public Health, 310003, Hangzhou, Zhejiang Province, China", 
            "Key Laboratory of Organ Transplantation, 310003, Hangzhou, Zhejiang Province, China"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Yang", 
        "givenName": "Zhengjie", 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Key Laboratory of Organ Transplantation, 310003, 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, 310003, Hangzhou, China", 
            "Key Laboratory of Combined Multi-organ Transplantation, Ministry of Public Health, 310003, Hangzhou, Zhejiang Province, China", 
            "Key Laboratory of Organ Transplantation, 310003, Hangzhou, Zhejiang Province, China"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Wen", 
        "givenName": "Xiaoyu", 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Key Laboratory of Organ Transplantation, 310003, 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, 310003, Hangzhou, China", 
            "Key Laboratory of Combined Multi-organ Transplantation, Ministry of Public Health, 310003, Hangzhou, Zhejiang Province, China", 
            "Key Laboratory of Organ Transplantation, 310003, Hangzhou, Zhejiang Province, 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 Organ Transplantation, 310003, 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, 310003, Hangzhou, China", 
            "Key Laboratory of Combined Multi-organ Transplantation, Ministry of Public Health, 310003, Hangzhou, Zhejiang Province, China", 
            "Key Laboratory of Organ Transplantation, 310003, Hangzhou, Zhejiang Province, 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": "Department of Surgery, The Second Affiliated Hospital and Yuying Children\u2019s Hospital of Wenzhou Medical University, 325027, Wenzhou, China", 
          "id": "http://www.grid.ac/institutes/grid.417384.d", 
          "name": [
            "Department of Surgery, The Second Affiliated Hospital and Yuying Children\u2019s Hospital of Wenzhou Medical University, 325027, Wenzhou, China"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Shen", 
        "givenName": "Xian", 
        "id": "sg:person.01130135040.53", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01130135040.53"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Key Laboratory of Organ Transplantation, 310003, 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, 310003, Hangzhou, China", 
            "Key Laboratory of Combined Multi-organ Transplantation, Ministry of Public Health, 310003, Hangzhou, Zhejiang Province, China", 
            "Key Laboratory of Organ Transplantation, 310003, Hangzhou, Zhejiang Province, 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 Organ Transplantation, 310003, 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, 310003, Hangzhou, China", 
            "Key Laboratory of Combined Multi-organ Transplantation, Ministry of Public Health, 310003, Hangzhou, Zhejiang Province, China", 
            "Key Laboratory of Organ Transplantation, 310003, Hangzhou, Zhejiang Province, 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/nmeth.3047", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1003995336", 
          "https://doi.org/10.1038/nmeth.3047"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/nature15697", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1050873736", 
          "https://doi.org/10.1038/nature15697"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/nature13166", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1027499136", 
          "https://doi.org/10.1038/nature13166"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1186/s13045-017-0424-0", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1084251884", 
          "https://doi.org/10.1186/s13045-017-0424-0"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/labinvest.2013.151", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1038072262", 
          "https://doi.org/10.1038/labinvest.2013.151"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/ng.3113", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1042448668", 
          "https://doi.org/10.1038/ng.3113"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/onc.2011.152", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1002149281", 
          "https://doi.org/10.1038/onc.2011.152"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/ncomms14483", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1084128804", 
          "https://doi.org/10.1038/ncomms14483"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/nrgastro.2014.157", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1003292531", 
          "https://doi.org/10.1038/nrgastro.2014.157"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/srep03012", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1040593671", 
          "https://doi.org/10.1038/srep03012"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/nm.4219", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1028123998", 
          "https://doi.org/10.1038/nm.4219"
        ], 
        "type": "CreativeWork"
      }
    ], 
    "datePublished": "2018-02-21", 
    "datePublishedReg": "2018-02-21", 
    "description": "The genome-wide clustered regularly interspaced short palindromic repeats (CRISPR) screen is a powerful tool used to identify therapeutic targets that can be harnessed for cancer treatment. This study aimed to assess the efficacy of genome-wide CRISPR screening to identify druggable genes associated with sorafenib-treated hepatocellular carcinoma (HCC). A genome-scale CRISPR knockout (GeCKO v2) library containing 123,411 single guide RNAs (sgRNAs) was used to identify loss-of-function mutations conferring sorafenib resistance upon HCC cells. Resistance gene screens identified SGOL1 as an indicator of prognosis of patients treated with sorafenib. Of the 19,050 genes tested, the knockout screen identified inhibition of SGOL1 expression as the most-effective genetic suppressor of sorafenib activity. Analysis of the survival of 210 patients with HCC after hepatic resection revealed that high SGOL1 expression shortened overall survival (P\u2009=\u20090.021). Further, matched pairs analysis of the TCGA database revealed that SGOL1 is differentially expressed. When we used a lentivirus Cas9 vector to determine the effect of targeting SGOL1 with a specific sgRNA in HCC cells, we found that SGOL1 expression was efficiently inhibited and that loss of SGOL1 was associated with sorafenib resistance. Further, loss of SGOL1 from HCC cell decreased the cytotoxicity of sorafenib in vivo. We conclude that the CRISPR screen is a powerful tool for therapeutic target analysis of sorafenib treatment and that SGOL1 serves as a druggable target for HCC treated with sorafenib and an indicator of prognosis.", 
    "genre": "article", 
    "id": "sg:pub.10.1038/s41374-018-0027-6", 
    "isAccessibleForFree": true, 
    "isPartOf": [
      {
        "id": "sg:journal.1017964", 
        "issn": [
          "0023-6837", 
          "1530-0307"
        ], 
        "name": "Laboratory Investigation", 
        "publisher": "Springer Nature", 
        "type": "Periodical"
      }, 
      {
        "issueNumber": "6", 
        "type": "PublicationIssue"
      }, 
      {
        "type": "PublicationVolume", 
        "volumeNumber": "98"
      }
    ], 
    "keywords": [
      "indicator of prognosis", 
      "hepatocellular carcinoma", 
      "HCC cells", 
      "single guide RNAs", 
      "sorafenib resistance", 
      "sorafenib-treated hepatocellular carcinoma", 
      "druggable targets", 
      "cytotoxicity of sorafenib", 
      "CRISPR screens", 
      "hepatic resection", 
      "overall survival", 
      "repeat screens", 
      "sorafenib treatment", 
      "genome-wide CRISPR screen", 
      "short palindromic repeats (CRISPR) screens", 
      "therapeutic target", 
      "sorafenib activity", 
      "genome-wide CRISPR", 
      "sorafenib", 
      "TCGA database", 
      "specific single-guide RNAs", 
      "cancer treatment", 
      "knockout library", 
      "genetic suppressors", 
      "patients", 
      "prognosis", 
      "carcinoma", 
      "function mutations", 
      "knockout screens", 
      "guide RNA", 
      "SGOL1", 
      "druggable genes", 
      "gene screen", 
      "survival", 
      "treatment", 
      "pair analysis", 
      "cells", 
      "expression", 
      "powerful tool", 
      "genes", 
      "resection", 
      "target", 
      "efficacy", 
      "lentivirus", 
      "screen", 
      "target analysis", 
      "loss", 
      "vivo", 
      "inhibition", 
      "cytotoxicity", 
      "genome", 
      "CRISPR", 
      "resistance", 
      "suppressor", 
      "RNA", 
      "mutations", 
      "indicators", 
      "database", 
      "activity", 
      "analysis", 
      "study", 
      "effect", 
      "library", 
      "tool", 
      "vector"
    ], 
    "name": "Genome-wide CRISPR screen reveals SGOL1 as a druggable target of sorafenib-treated hepatocellular carcinoma", 
    "pagination": "734-744", 
    "productId": [
      {
        "name": "dimensions_id", 
        "type": "PropertyValue", 
        "value": [
          "pub.1101141666"
        ]
      }, 
      {
        "name": "doi", 
        "type": "PropertyValue", 
        "value": [
          "10.1038/s41374-018-0027-6"
        ]
      }, 
      {
        "name": "pubmed_id", 
        "type": "PropertyValue", 
        "value": [
          "29467456"
        ]
      }
    ], 
    "sameAs": [
      "https://doi.org/10.1038/s41374-018-0027-6", 
      "https://app.dimensions.ai/details/publication/pub.1101141666"
    ], 
    "sdDataset": "articles", 
    "sdDatePublished": "2022-10-01T06:44", 
    "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_768.jsonl", 
    "type": "ScholarlyArticle", 
    "url": "https://doi.org/10.1038/s41374-018-0027-6"
  }
]
 

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.10.1038/s41374-018-0027-6'

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

curl -H 'Accept: application/n-triples' 'https://scigraph.springernature.com/pub.10.1038/s41374-018-0027-6'

Turtle is a human-readable linked data format.

curl -H 'Accept: text/turtle' 'https://scigraph.springernature.com/pub.10.1038/s41374-018-0027-6'

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

curl -H 'Accept: application/rdf+xml' 'https://scigraph.springernature.com/pub.10.1038/s41374-018-0027-6'


 

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

318 TRIPLES      21 PREDICATES      116 URIs      97 LITERALS      22 BLANK NODES

Subject Predicate Object
1 sg:pub.10.1038/s41374-018-0027-6 schema:about N00ae10ac4abe400da97da25b336cb5f7
2 N141bd46411bc4f1bb5725cf0591d8bc8
3 N26fed2f3a63b4cf8b0d7df9edcf7a8c0
4 N4c18d8bd56474d96a925da2a789ce89f
5 N55e16f1e19504a7498b893c3103f5e52
6 N686d7746e5ac4bc99ce8be1b8207001b
7 N697dcba215234bb8a711067ad87ad59b
8 N74911ca04ebd480cb06c153dd8d9875c
9 N839be7305f3d4ac3abf0f0ba8178b32e
10 Na7208242cb7145ec8916b6714a31d328
11 Nb0d2b307a2a843bc9dc6382796af9323
12 Nc64e8964518c420194b097cf9bebdb57
13 Ndaed309a6d554d2cae522c3abaa4d8fe
14 Ne8205974d0b248f49aa013833bc0f8d9
15 Ne8fe70874ce742efb6c66a80f6e2e72c
16 anzsrc-for:11
17 anzsrc-for:1112
18 schema:author N97aea9997c1545c6b2b4d10e50745731
19 schema:citation sg:pub.10.1038/labinvest.2013.151
20 sg:pub.10.1038/nature13166
21 sg:pub.10.1038/nature15697
22 sg:pub.10.1038/ncomms14483
23 sg:pub.10.1038/ng.3113
24 sg:pub.10.1038/nm.4219
25 sg:pub.10.1038/nmeth.3047
26 sg:pub.10.1038/nrgastro.2014.157
27 sg:pub.10.1038/onc.2011.152
28 sg:pub.10.1038/srep03012
29 sg:pub.10.1186/s13045-017-0424-0
30 schema:datePublished 2018-02-21
31 schema:datePublishedReg 2018-02-21
32 schema:description The genome-wide clustered regularly interspaced short palindromic repeats (CRISPR) screen is a powerful tool used to identify therapeutic targets that can be harnessed for cancer treatment. This study aimed to assess the efficacy of genome-wide CRISPR screening to identify druggable genes associated with sorafenib-treated hepatocellular carcinoma (HCC). A genome-scale CRISPR knockout (GeCKO v2) library containing 123,411 single guide RNAs (sgRNAs) was used to identify loss-of-function mutations conferring sorafenib resistance upon HCC cells. Resistance gene screens identified SGOL1 as an indicator of prognosis of patients treated with sorafenib. Of the 19,050 genes tested, the knockout screen identified inhibition of SGOL1 expression as the most-effective genetic suppressor of sorafenib activity. Analysis of the survival of 210 patients with HCC after hepatic resection revealed that high SGOL1 expression shortened overall survival (P = 0.021). Further, matched pairs analysis of the TCGA database revealed that SGOL1 is differentially expressed. When we used a lentivirus Cas9 vector to determine the effect of targeting SGOL1 with a specific sgRNA in HCC cells, we found that SGOL1 expression was efficiently inhibited and that loss of SGOL1 was associated with sorafenib resistance. Further, loss of SGOL1 from HCC cell decreased the cytotoxicity of sorafenib in vivo. We conclude that the CRISPR screen is a powerful tool for therapeutic target analysis of sorafenib treatment and that SGOL1 serves as a druggable target for HCC treated with sorafenib and an indicator of prognosis.
33 schema:genre article
34 schema:isAccessibleForFree true
35 schema:isPartOf N65bef62c63ca4a6da156d8bb977d5de2
36 Nea9b1885bba04fccb2d7c6442d85805d
37 sg:journal.1017964
38 schema:keywords CRISPR
39 CRISPR screens
40 HCC cells
41 RNA
42 SGOL1
43 TCGA database
44 activity
45 analysis
46 cancer treatment
47 carcinoma
48 cells
49 cytotoxicity
50 cytotoxicity of sorafenib
51 database
52 druggable genes
53 druggable targets
54 effect
55 efficacy
56 expression
57 function mutations
58 gene screen
59 genes
60 genetic suppressors
61 genome
62 genome-wide CRISPR
63 genome-wide CRISPR screen
64 guide RNA
65 hepatic resection
66 hepatocellular carcinoma
67 indicator of prognosis
68 indicators
69 inhibition
70 knockout library
71 knockout screens
72 lentivirus
73 library
74 loss
75 mutations
76 overall survival
77 pair analysis
78 patients
79 powerful tool
80 prognosis
81 repeat screens
82 resection
83 resistance
84 screen
85 short palindromic repeats (CRISPR) screens
86 single guide RNAs
87 sorafenib
88 sorafenib activity
89 sorafenib resistance
90 sorafenib treatment
91 sorafenib-treated hepatocellular carcinoma
92 specific single-guide RNAs
93 study
94 suppressor
95 survival
96 target
97 target analysis
98 therapeutic target
99 tool
100 treatment
101 vector
102 vivo
103 schema:name Genome-wide CRISPR screen reveals SGOL1 as a druggable target of sorafenib-treated hepatocellular carcinoma
104 schema:pagination 734-744
105 schema:productId N14b3e24b3c474e75ba98610f68f20d49
106 N232d35d9fc7e40d1bd91dc86e9c3b74e
107 N7952ac40ade74a6c927d6f263cfac13f
108 schema:sameAs https://app.dimensions.ai/details/publication/pub.1101141666
109 https://doi.org/10.1038/s41374-018-0027-6
110 schema:sdDatePublished 2022-10-01T06:44
111 schema:sdLicense https://scigraph.springernature.com/explorer/license/
112 schema:sdPublisher Nfa0256c663c5411ba32beff6cbc0f63b
113 schema:url https://doi.org/10.1038/s41374-018-0027-6
114 sgo:license sg:explorer/license/
115 sgo:sdDataset articles
116 rdf:type schema:ScholarlyArticle
117 N00ae10ac4abe400da97da25b336cb5f7 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
118 schema:name Mice, Inbred BALB C
119 rdf:type schema:DefinedTerm
120 N04da1242a016475eb75a87af6c9a2cfb rdf:first N5cb29be4ced84158a0b174546c842501
121 rdf:rest N6c143ae96a2f4ada96c1e0b3e8418ebf
122 N141bd46411bc4f1bb5725cf0591d8bc8 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
123 schema:name Mice
124 rdf:type schema:DefinedTerm
125 N14b3e24b3c474e75ba98610f68f20d49 schema:name pubmed_id
126 schema:value 29467456
127 rdf:type schema:PropertyValue
128 N1a5ab3a8f93b40cb8ca7adb5d2a04220 rdf:first sg:person.014717003557.61
129 rdf:rest N6b331ed430ee41e3921272ad0b3e2136
130 N232d35d9fc7e40d1bd91dc86e9c3b74e schema:name doi
131 schema:value 10.1038/s41374-018-0027-6
132 rdf:type schema:PropertyValue
133 N26fed2f3a63b4cf8b0d7df9edcf7a8c0 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
134 schema:name Animals
135 rdf:type schema:DefinedTerm
136 N4c18d8bd56474d96a925da2a789ce89f schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
137 schema:name Sorafenib
138 rdf:type schema:DefinedTerm
139 N546c3177129346d69a49d6769d02db46 rdf:first sg:person.0707241735.24
140 rdf:rest N6cd1fbda12e44696b0e8c6c48ec4b872
141 N55e16f1e19504a7498b893c3103f5e52 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
142 schema:name Cell Cycle Proteins
143 rdf:type schema:DefinedTerm
144 N5cb29be4ced84158a0b174546c842501 schema:affiliation grid-institutes:grid.452661.2
145 schema:familyName Wen
146 schema:givenName Xiaoyu
147 rdf:type schema:Person
148 N640a445f59bd4f7f9d28221b0232cdf2 rdf:first sg:person.012354763701.47
149 rdf:rest N546c3177129346d69a49d6769d02db46
150 N65bef62c63ca4a6da156d8bb977d5de2 schema:volumeNumber 98
151 rdf:type schema:PublicationVolume
152 N686d7746e5ac4bc99ce8be1b8207001b schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
153 schema:name Genome-Wide Association Study
154 rdf:type schema:DefinedTerm
155 N697dcba215234bb8a711067ad87ad59b schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
156 schema:name Gene Knockdown Techniques
157 rdf:type schema:DefinedTerm
158 N6b331ed430ee41e3921272ad0b3e2136 rdf:first sg:person.0640501242.51
159 rdf:rest rdf:nil
160 N6c143ae96a2f4ada96c1e0b3e8418ebf rdf:first sg:person.0753155421.39
161 rdf:rest N955b5239529341b9b7e406463dedbe82
162 N6cd1fbda12e44696b0e8c6c48ec4b872 rdf:first sg:person.01152647226.17
163 rdf:rest N7becd71eb6494e0aa45f6f0104aa3525
164 N74911ca04ebd480cb06c153dd8d9875c schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
165 schema:name Liver Neoplasms
166 rdf:type schema:DefinedTerm
167 N7900754fce6a439fb4fb129958531d5a rdf:first Nfdc28b61dddd4155a066c9a164d41665
168 rdf:rest N04da1242a016475eb75a87af6c9a2cfb
169 N7952ac40ade74a6c927d6f263cfac13f schema:name dimensions_id
170 schema:value pub.1101141666
171 rdf:type schema:PropertyValue
172 N7becd71eb6494e0aa45f6f0104aa3525 rdf:first sg:person.01104534026.18
173 rdf:rest N7900754fce6a439fb4fb129958531d5a
174 N839be7305f3d4ac3abf0f0ba8178b32e schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
175 schema:name Drug Resistance, Neoplasm
176 rdf:type schema:DefinedTerm
177 N955b5239529341b9b7e406463dedbe82 rdf:first sg:person.0657720126.04
178 rdf:rest Nc33916d971654b2395bd4c2f140e622b
179 N97aea9997c1545c6b2b4d10e50745731 rdf:first sg:person.014250455551.61
180 rdf:rest Ncde5ae4fed794733bcdbc707fb11ea2f
181 Na7208242cb7145ec8916b6714a31d328 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
182 schema:name Carcinoma, Hepatocellular
183 rdf:type schema:DefinedTerm
184 Nb0d2b307a2a843bc9dc6382796af9323 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
185 schema:name Antineoplastic Agents
186 rdf:type schema:DefinedTerm
187 Nc33916d971654b2395bd4c2f140e622b rdf:first sg:person.01130135040.53
188 rdf:rest N1a5ab3a8f93b40cb8ca7adb5d2a04220
189 Nc64e8964518c420194b097cf9bebdb57 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
190 schema:name Humans
191 rdf:type schema:DefinedTerm
192 Ncde5ae4fed794733bcdbc707fb11ea2f rdf:first sg:person.01157531127.42
193 rdf:rest N640a445f59bd4f7f9d28221b0232cdf2
194 Ndaed309a6d554d2cae522c3abaa4d8fe schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
195 schema:name Clustered Regularly Interspaced Short Palindromic Repeats
196 rdf:type schema:DefinedTerm
197 Ne8205974d0b248f49aa013833bc0f8d9 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
198 schema:name Cell Line, Tumor
199 rdf:type schema:DefinedTerm
200 Ne8fe70874ce742efb6c66a80f6e2e72c schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
201 schema:name Prognosis
202 rdf:type schema:DefinedTerm
203 Nea9b1885bba04fccb2d7c6442d85805d schema:issueNumber 6
204 rdf:type schema:PublicationIssue
205 Nfa0256c663c5411ba32beff6cbc0f63b schema:name Springer Nature - SN SciGraph project
206 rdf:type schema:Organization
207 Nfdc28b61dddd4155a066c9a164d41665 schema:affiliation grid-institutes:grid.452661.2
208 schema:familyName Yang
209 schema:givenName Zhengjie
210 rdf:type schema:Person
211 anzsrc-for:11 schema:inDefinedTermSet anzsrc-for:
212 schema:name Medical and Health Sciences
213 rdf:type schema:DefinedTerm
214 anzsrc-for:1112 schema:inDefinedTermSet anzsrc-for:
215 schema:name Oncology and Carcinogenesis
216 rdf:type schema:DefinedTerm
217 sg:journal.1017964 schema:issn 0023-6837
218 1530-0307
219 schema:name Laboratory Investigation
220 schema:publisher Springer Nature
221 rdf:type schema:Periodical
222 sg:person.01104534026.18 schema:affiliation grid-institutes:grid.452661.2
223 schema:familyName Xiao
224 schema:givenName Heng
225 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01104534026.18
226 rdf:type schema:Person
227 sg:person.01130135040.53 schema:affiliation grid-institutes:grid.417384.d
228 schema:familyName Shen
229 schema:givenName Xian
230 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01130135040.53
231 rdf:type schema:Person
232 sg:person.01152647226.17 schema:affiliation grid-institutes:grid.452661.2
233 schema:familyName Cheng
234 schema:givenName Shaobing
235 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01152647226.17
236 rdf:type schema:Person
237 sg:person.01157531127.42 schema:affiliation grid-institutes:grid.452661.2
238 schema:familyName He
239 schema:givenName Bin
240 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01157531127.42
241 rdf:type schema:Person
242 sg:person.012354763701.47 schema:affiliation grid-institutes:grid.452661.2
243 schema:familyName Yang
244 schema:givenName Beng
245 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.012354763701.47
246 rdf:type schema:Person
247 sg:person.014250455551.61 schema:affiliation grid-institutes:grid.452661.2
248 schema:familyName Sun
249 schema:givenName Weijian
250 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.014250455551.61
251 rdf:type schema:Person
252 sg:person.014717003557.61 schema:affiliation grid-institutes:grid.452661.2
253 schema:familyName Wu
254 schema:givenName Jian
255 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.014717003557.61
256 rdf:type schema:Person
257 sg:person.0640501242.51 schema:affiliation grid-institutes:grid.452661.2
258 schema:familyName Zheng
259 schema:givenName Shusen
260 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0640501242.51
261 rdf:type schema:Person
262 sg:person.0657720126.04 schema:affiliation grid-institutes:grid.452661.2
263 schema:familyName Xie
264 schema:givenName Haiyang
265 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0657720126.04
266 rdf:type schema:Person
267 sg:person.0707241735.24 schema:affiliation grid-institutes:grid.452661.2
268 schema:familyName Hu
269 schema:givenName Wendi
270 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0707241735.24
271 rdf:type schema:Person
272 sg:person.0753155421.39 schema:affiliation grid-institutes:grid.452661.2
273 schema:familyName Zhou
274 schema:givenName Lin
275 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0753155421.39
276 rdf:type schema:Person
277 sg:pub.10.1038/labinvest.2013.151 schema:sameAs https://app.dimensions.ai/details/publication/pub.1038072262
278 https://doi.org/10.1038/labinvest.2013.151
279 rdf:type schema:CreativeWork
280 sg:pub.10.1038/nature13166 schema:sameAs https://app.dimensions.ai/details/publication/pub.1027499136
281 https://doi.org/10.1038/nature13166
282 rdf:type schema:CreativeWork
283 sg:pub.10.1038/nature15697 schema:sameAs https://app.dimensions.ai/details/publication/pub.1050873736
284 https://doi.org/10.1038/nature15697
285 rdf:type schema:CreativeWork
286 sg:pub.10.1038/ncomms14483 schema:sameAs https://app.dimensions.ai/details/publication/pub.1084128804
287 https://doi.org/10.1038/ncomms14483
288 rdf:type schema:CreativeWork
289 sg:pub.10.1038/ng.3113 schema:sameAs https://app.dimensions.ai/details/publication/pub.1042448668
290 https://doi.org/10.1038/ng.3113
291 rdf:type schema:CreativeWork
292 sg:pub.10.1038/nm.4219 schema:sameAs https://app.dimensions.ai/details/publication/pub.1028123998
293 https://doi.org/10.1038/nm.4219
294 rdf:type schema:CreativeWork
295 sg:pub.10.1038/nmeth.3047 schema:sameAs https://app.dimensions.ai/details/publication/pub.1003995336
296 https://doi.org/10.1038/nmeth.3047
297 rdf:type schema:CreativeWork
298 sg:pub.10.1038/nrgastro.2014.157 schema:sameAs https://app.dimensions.ai/details/publication/pub.1003292531
299 https://doi.org/10.1038/nrgastro.2014.157
300 rdf:type schema:CreativeWork
301 sg:pub.10.1038/onc.2011.152 schema:sameAs https://app.dimensions.ai/details/publication/pub.1002149281
302 https://doi.org/10.1038/onc.2011.152
303 rdf:type schema:CreativeWork
304 sg:pub.10.1038/srep03012 schema:sameAs https://app.dimensions.ai/details/publication/pub.1040593671
305 https://doi.org/10.1038/srep03012
306 rdf:type schema:CreativeWork
307 sg:pub.10.1186/s13045-017-0424-0 schema:sameAs https://app.dimensions.ai/details/publication/pub.1084251884
308 https://doi.org/10.1186/s13045-017-0424-0
309 rdf:type schema:CreativeWork
310 grid-institutes:grid.417384.d schema:alternateName Department of Surgery, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, 325027, Wenzhou, China
311 schema:name Department of Surgery, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, 325027, Wenzhou, China
312 rdf:type schema:Organization
313 grid-institutes:grid.452661.2 schema:alternateName Key Laboratory of Organ Transplantation, 310003, Hangzhou, Zhejiang Province, China
314 schema:name Department of Surgery, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, 325027, Wenzhou, China
315 Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, 310003, Hangzhou, China
316 Key Laboratory of Combined Multi-organ Transplantation, Ministry of Public Health, 310003, Hangzhou, Zhejiang Province, China
317 Key Laboratory of Organ Transplantation, 310003, Hangzhou, Zhejiang Province, China
318 rdf:type schema:Organization
 




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


...