MicroRNAs define distinct human neuroblastoma cell phenotypes and regulate their differentiation and tumorigenicity View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2014-12

AUTHORS

Leleesha Samaraweera, Kathryn B Grandinetti, Ruojun Huang, Barbara A Spengler, Robert A Ross

ABSTRACT

BACKGROUND: Neuroblastoma (NB) is the most common extracranial solid tumor in children. NB tumors and derived cell lines are phenotypically heterogeneous. Cell lines are classified by phenotype, each having distinct differentiation and tumorigenic properties. The neuroblastic phenotype is tumorigenic, has neuronal features and includes stem cells (I-cells) and neuronal cells (N-cells). The non-neuronal phenotype (S-cell) comprises cells that are non-tumorigenic with features of glial/smooth muscle precursor cells. This study identified miRNAs associated with each distinct cell phenotypes and investigated their role in regulating associated differentiation and tumorigenic properties. METHODS: A miRNA microarray was performed on the three cell phenotypes and expression verified by qRT-PCR. miRNAs specific for certain cell phenotypes were modulated using miRNA inhibitors or stable transfection. Neuronal differentiation was induced by RA; non-neuronal differentiation by BrdU. Changes in tumorigenicity were assayed by soft agar colony forming ability. N-myc binding to miR-375 promoter was assayed by chromatin-immunoprecipitation. RESULTS: Unsupervised hierarchical clustering of miRNA microarray data segregated neuroblastic and non-neuronal cell lines and showed that specific miRNAs define each phenotype. qRT-PCR validation confirmed that increased levels of miR-21, miR-221 and miR-335 are associated with the non-neuronal phenotype, whereas increased levels of miR-124 and miR-375 are exclusive to neuroblastic cells. Downregulation of miR-335 in non-neuronal cells modulates expression levels of HAND1 and JAG1, known modulators of neuronal differentiation. Overexpression of miR-124 in stem cells induces terminal neuronal differentiation with reduced malignancy. Expression of miR-375 is exclusive for N-myc-expressing neuroblastic cells and is regulated by N-myc. Moreover, miR-375 downregulates expression of the neuronal-specific RNA binding protein HuD. CONCLUSIONS: Thus, miRNAs define distinct NB cell phenotypes. Increased levels of miR-21, miR-221 and miR-335 characterize the non-neuronal, non-malignant phenotype and miR-335 maintains the non-neuronal features possibly by blocking neuronal differentiation. miR-124 induces terminal neuronal differentiation with reduction in malignancy. Data suggest N-myc inhibits neuronal differentiation of neuroblastic cells possibly by upregulating miR-375 which, in turn, suppresses HuD. As tumor differentiation state is highly predictive of patient survival, the involvement of these miRNAs with NB differentiation and tumorigenic state could be exploited in the development of novel therapeutic strategies for this enigmatic childhood cancer. More... »

PAGES

309

Identifiers

URI

http://scigraph.springernature.com/pub.10.1186/1471-2407-14-309

DOI

http://dx.doi.org/10.1186/1471-2407-14-309

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1048033679

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/24885481


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/2008/1112", 
        "inDefinedTermSet": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/", 
        "name": "Oncology and Carcinogenesis", 
        "type": "DefinedTerm"
      }, 
      {
        "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"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Brain Neoplasms", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Carcinogenesis", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Cell Differentiation", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Cell Line, Tumor", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Child", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "ELAV Proteins", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "ELAV-Like Protein 4", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Gene Expression Regulation, Neoplastic", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Humans", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "MicroRNAs", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Microarray Analysis", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Neural Stem Cells", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Neuroblastoma", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Phenotype", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "RNA-Binding Proteins", 
        "type": "DefinedTerm"
      }
    ], 
    "author": [
      {
        "affiliation": {
          "alternateName": "Albert Einstein College of Medicine", 
          "id": "https://www.grid.ac/institutes/grid.251993.5", 
          "name": [
            "Albert Einstein College of Medicine, 1300, Morris Park Ave, 10461, Bronx, NY, USA"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Samaraweera", 
        "givenName": "Leleesha", 
        "id": "sg:person.01275212530.13", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01275212530.13"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Genomics Institute of the Novartis Research Foundation", 
          "id": "https://www.grid.ac/institutes/grid.418185.1", 
          "name": [
            "Genomics Institute of the Novartis Research Foundation, San Diego, CA, USA"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Grandinetti", 
        "givenName": "Kathryn B", 
        "id": "sg:person.01104000267.79", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01104000267.79"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Consolidated Edison (United States)", 
          "id": "https://www.grid.ac/institutes/grid.453554.6", 
          "name": [
            "Edison, NJ, USA"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Huang", 
        "givenName": "Ruojun", 
        "id": "sg:person.0744113216.27", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0744113216.27"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Fordham University", 
          "id": "https://www.grid.ac/institutes/grid.256023.0", 
          "name": [
            "Fordham University, 441 E. Fordham Road, 10458, Bronx, NY, USA"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Spengler", 
        "givenName": "Barbara A", 
        "id": "sg:person.01040304662.31", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01040304662.31"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Fordham University", 
          "id": "https://www.grid.ac/institutes/grid.256023.0", 
          "name": [
            "Fordham University, 441 E. Fordham Road, 10458, Bronx, NY, USA"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Ross", 
        "givenName": "Robert A", 
        "id": "sg:person.01170011620.41", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01170011620.41"
        ], 
        "type": "Person"
      }
    ], 
    "citation": [
      {
        "id": "https://doi.org/10.1371/journal.pone.0005033", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1004731588"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1371/journal.pone.0007850", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1013228564"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1093/carcin/bgs114", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1014491814"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1128/mcb.01694-08", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1017449151"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1056/nejm199910143411601", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1017604054"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1517/14728222.2010.510136", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1019231404"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1128/mcb.24.13.5923-5936.2004", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1021126403"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1128/mcb.00316-10", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1023616678"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1074/jbc.275.13.9186", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1024169911"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1074/jbc.m312663200", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1025867111"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/j.semcancer.2011.07.001", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1028098297"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/sj.onc.1209095", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1031323858", 
          "https://doi.org/10.1038/sj.onc.1209095"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/sj.onc.1209095", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1031323858", 
          "https://doi.org/10.1038/sj.onc.1209095"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/sj.onc.1209095", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1031323858", 
          "https://doi.org/10.1038/sj.onc.1209095"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1002/ijc.23153", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1033649705"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1593/neo.04310", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1034584550"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1158/0008-5472.can-06-3667", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1041483621"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1002/pbc.24433", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1042533154"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1073/pnas.83.16.5929", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1042712023"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/nm1010-1079", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1043279292", 
          "https://doi.org/10.1038/nm1010-1079"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1158/0008-5472.can-10-0970", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1044643438"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1073/pnas.0511041103", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1046042632"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/nrn1847", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1047057402", 
          "https://doi.org/10.1038/nrn1847"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/nrn1847", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1047057402", 
          "https://doi.org/10.1038/nrn1847"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.5772/29142", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1047215286"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1634/stemcells.2005-0441", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1048521174"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/j.semcancer.2006.04.006", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1050668481"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1371/journal.pone.0023461", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1050867137"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/313404a0", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1051468821", 
          "https://doi.org/10.1038/313404a0"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1006/dbio.1999.9450", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1051936861"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.2174/138161209787315837", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1069166847"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.4161/cbt.9.6.10894", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1072295713"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1093/jnci/73.2.405", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1081843234"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://app.dimensions.ai/details/publication/pub.1083224246", 
        "type": "CreativeWork"
      }
    ], 
    "datePublished": "2014-12", 
    "datePublishedReg": "2014-12-01", 
    "description": "BACKGROUND: Neuroblastoma (NB) is the most common extracranial solid tumor in children. NB tumors and derived cell lines are phenotypically heterogeneous. Cell lines are classified by phenotype, each having distinct differentiation and tumorigenic properties. The neuroblastic phenotype is tumorigenic, has neuronal features and includes stem cells (I-cells) and neuronal cells (N-cells). The non-neuronal phenotype (S-cell) comprises cells that are non-tumorigenic with features of glial/smooth muscle precursor cells. This study identified miRNAs associated with each distinct cell phenotypes and investigated their role in regulating associated differentiation and tumorigenic properties.\nMETHODS: A miRNA microarray was performed on the three cell phenotypes and expression verified by qRT-PCR. miRNAs specific for certain cell phenotypes were modulated using miRNA inhibitors or stable transfection. Neuronal differentiation was induced by RA; non-neuronal differentiation by BrdU. Changes in tumorigenicity were assayed by soft agar colony forming ability. N-myc binding to miR-375 promoter was assayed by chromatin-immunoprecipitation.\nRESULTS: Unsupervised hierarchical clustering of miRNA microarray data segregated neuroblastic and non-neuronal cell lines and showed that specific miRNAs define each phenotype. qRT-PCR validation confirmed that increased levels of miR-21, miR-221 and miR-335 are associated with the non-neuronal phenotype, whereas increased levels of miR-124 and miR-375 are exclusive to neuroblastic cells. Downregulation of miR-335 in non-neuronal cells modulates expression levels of HAND1 and JAG1, known modulators of neuronal differentiation. Overexpression of miR-124 in stem cells induces terminal neuronal differentiation with reduced malignancy. Expression of miR-375 is exclusive for N-myc-expressing neuroblastic cells and is regulated by N-myc. Moreover, miR-375 downregulates expression of the neuronal-specific RNA binding protein HuD.\nCONCLUSIONS: Thus, miRNAs define distinct NB cell phenotypes. Increased levels of miR-21, miR-221 and miR-335 characterize the non-neuronal, non-malignant phenotype and miR-335 maintains the non-neuronal features possibly by blocking neuronal differentiation. miR-124 induces terminal neuronal differentiation with reduction in malignancy. Data suggest N-myc inhibits neuronal differentiation of neuroblastic cells possibly by upregulating miR-375 which, in turn, suppresses HuD. As tumor differentiation state is highly predictive of patient survival, the involvement of these miRNAs with NB differentiation and tumorigenic state could be exploited in the development of novel therapeutic strategies for this enigmatic childhood cancer.", 
    "genre": "research_article", 
    "id": "sg:pub.10.1186/1471-2407-14-309", 
    "inLanguage": [
      "en"
    ], 
    "isAccessibleForFree": true, 
    "isFundedItemOf": [
      {
        "id": "sg:grant.2473642", 
        "type": "MonetaryGrant"
      }
    ], 
    "isPartOf": [
      {
        "id": "sg:journal.1024632", 
        "issn": [
          "1471-2407"
        ], 
        "name": "BMC Cancer", 
        "type": "Periodical"
      }, 
      {
        "issueNumber": "1", 
        "type": "PublicationIssue"
      }, 
      {
        "type": "PublicationVolume", 
        "volumeNumber": "14"
      }
    ], 
    "name": "MicroRNAs define distinct human neuroblastoma cell phenotypes and regulate their differentiation and tumorigenicity", 
    "pagination": "309", 
    "productId": [
      {
        "name": "readcube_id", 
        "type": "PropertyValue", 
        "value": [
          "e4d2c2ef509fc2a252b686bcc04af697737c6f416b138344039cc8ca594d5551"
        ]
      }, 
      {
        "name": "pubmed_id", 
        "type": "PropertyValue", 
        "value": [
          "24885481"
        ]
      }, 
      {
        "name": "nlm_unique_id", 
        "type": "PropertyValue", 
        "value": [
          "100967800"
        ]
      }, 
      {
        "name": "doi", 
        "type": "PropertyValue", 
        "value": [
          "10.1186/1471-2407-14-309"
        ]
      }, 
      {
        "name": "dimensions_id", 
        "type": "PropertyValue", 
        "value": [
          "pub.1048033679"
        ]
      }
    ], 
    "sameAs": [
      "https://doi.org/10.1186/1471-2407-14-309", 
      "https://app.dimensions.ai/details/publication/pub.1048033679"
    ], 
    "sdDataset": "articles", 
    "sdDatePublished": "2019-04-10T15:02", 
    "sdLicense": "https://scigraph.springernature.com/explorer/license/", 
    "sdPublisher": {
      "name": "Springer Nature - SN SciGraph project", 
      "type": "Organization"
    }, 
    "sdSource": "s3://com-uberresearch-data-dimensions-target-20181106-alternative/cleanup/v134/2549eaecd7973599484d7c17b260dba0a4ecb94b/merge/v9/a6c9fde33151104705d4d7ff012ea9563521a3ce/jats-lookup/v90/0000000001_0000000264/records_8663_00000516.jsonl", 
    "type": "ScholarlyArticle", 
    "url": "http://link.springer.com/10.1186%2F1471-2407-14-309"
  }
]
 

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.10.1186/1471-2407-14-309'

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

curl -H 'Accept: application/n-triples' 'https://scigraph.springernature.com/pub.10.1186/1471-2407-14-309'

Turtle is a human-readable linked data format.

curl -H 'Accept: text/turtle' 'https://scigraph.springernature.com/pub.10.1186/1471-2407-14-309'

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

curl -H 'Accept: application/rdf+xml' 'https://scigraph.springernature.com/pub.10.1186/1471-2407-14-309'


 

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

263 TRIPLES      21 PREDICATES      75 URIs      36 LITERALS      24 BLANK NODES

Subject Predicate Object
1 sg:pub.10.1186/1471-2407-14-309 schema:about N0925dfbdde3249e9a2ee2222b552ecb5
2 N170585d938b043369aeb1dd147a0bced
3 N3166871ed96445848dbccdc3a17a4874
4 N316f1b9f42e84fbca72d257bf8a5665a
5 N447e11a0cac2461481e133bea6beb63e
6 N60f652801bc244a5802a5caff36e1000
7 N7f3735433d584ed5a17c3be7d6b66b16
8 Nc3da5a59c33d49f29e6570976b0fb793
9 Nc7b07b124ea14d67ad1812ddc2f506eb
10 Nda4bc26ba69a465996b0064be07d77c9
11 Nddab09989668414ba302e94a02e07272
12 Ndece3df063804687bbfc1c6282f5fd36
13 Ne13ec863873c4f888d566b021d8b85cc
14 Neacef8cf32684a34ad6850483ec3833e
15 Nfb304f51db07484b824ed6d09316f764
16 anzsrc-for:11
17 anzsrc-for:1112
18 schema:author N95120fc9459b44e082d39d0369a44618
19 schema:citation sg:pub.10.1038/313404a0
20 sg:pub.10.1038/nm1010-1079
21 sg:pub.10.1038/nrn1847
22 sg:pub.10.1038/sj.onc.1209095
23 https://app.dimensions.ai/details/publication/pub.1083224246
24 https://doi.org/10.1002/ijc.23153
25 https://doi.org/10.1002/pbc.24433
26 https://doi.org/10.1006/dbio.1999.9450
27 https://doi.org/10.1016/j.semcancer.2006.04.006
28 https://doi.org/10.1016/j.semcancer.2011.07.001
29 https://doi.org/10.1056/nejm199910143411601
30 https://doi.org/10.1073/pnas.0511041103
31 https://doi.org/10.1073/pnas.83.16.5929
32 https://doi.org/10.1074/jbc.275.13.9186
33 https://doi.org/10.1074/jbc.m312663200
34 https://doi.org/10.1093/carcin/bgs114
35 https://doi.org/10.1093/jnci/73.2.405
36 https://doi.org/10.1128/mcb.00316-10
37 https://doi.org/10.1128/mcb.01694-08
38 https://doi.org/10.1128/mcb.24.13.5923-5936.2004
39 https://doi.org/10.1158/0008-5472.can-06-3667
40 https://doi.org/10.1158/0008-5472.can-10-0970
41 https://doi.org/10.1371/journal.pone.0005033
42 https://doi.org/10.1371/journal.pone.0007850
43 https://doi.org/10.1371/journal.pone.0023461
44 https://doi.org/10.1517/14728222.2010.510136
45 https://doi.org/10.1593/neo.04310
46 https://doi.org/10.1634/stemcells.2005-0441
47 https://doi.org/10.2174/138161209787315837
48 https://doi.org/10.4161/cbt.9.6.10894
49 https://doi.org/10.5772/29142
50 schema:datePublished 2014-12
51 schema:datePublishedReg 2014-12-01
52 schema:description BACKGROUND: Neuroblastoma (NB) is the most common extracranial solid tumor in children. NB tumors and derived cell lines are phenotypically heterogeneous. Cell lines are classified by phenotype, each having distinct differentiation and tumorigenic properties. The neuroblastic phenotype is tumorigenic, has neuronal features and includes stem cells (I-cells) and neuronal cells (N-cells). The non-neuronal phenotype (S-cell) comprises cells that are non-tumorigenic with features of glial/smooth muscle precursor cells. This study identified miRNAs associated with each distinct cell phenotypes and investigated their role in regulating associated differentiation and tumorigenic properties. METHODS: A miRNA microarray was performed on the three cell phenotypes and expression verified by qRT-PCR. miRNAs specific for certain cell phenotypes were modulated using miRNA inhibitors or stable transfection. Neuronal differentiation was induced by RA; non-neuronal differentiation by BrdU. Changes in tumorigenicity were assayed by soft agar colony forming ability. N-myc binding to miR-375 promoter was assayed by chromatin-immunoprecipitation. RESULTS: Unsupervised hierarchical clustering of miRNA microarray data segregated neuroblastic and non-neuronal cell lines and showed that specific miRNAs define each phenotype. qRT-PCR validation confirmed that increased levels of miR-21, miR-221 and miR-335 are associated with the non-neuronal phenotype, whereas increased levels of miR-124 and miR-375 are exclusive to neuroblastic cells. Downregulation of miR-335 in non-neuronal cells modulates expression levels of HAND1 and JAG1, known modulators of neuronal differentiation. Overexpression of miR-124 in stem cells induces terminal neuronal differentiation with reduced malignancy. Expression of miR-375 is exclusive for N-myc-expressing neuroblastic cells and is regulated by N-myc. Moreover, miR-375 downregulates expression of the neuronal-specific RNA binding protein HuD. CONCLUSIONS: Thus, miRNAs define distinct NB cell phenotypes. Increased levels of miR-21, miR-221 and miR-335 characterize the non-neuronal, non-malignant phenotype and miR-335 maintains the non-neuronal features possibly by blocking neuronal differentiation. miR-124 induces terminal neuronal differentiation with reduction in malignancy. Data suggest N-myc inhibits neuronal differentiation of neuroblastic cells possibly by upregulating miR-375 which, in turn, suppresses HuD. As tumor differentiation state is highly predictive of patient survival, the involvement of these miRNAs with NB differentiation and tumorigenic state could be exploited in the development of novel therapeutic strategies for this enigmatic childhood cancer.
53 schema:genre research_article
54 schema:inLanguage en
55 schema:isAccessibleForFree true
56 schema:isPartOf N5a6058343ac048fc92a1cfdd5a04fb85
57 N912bc41c926142b5963a572785b1764e
58 sg:journal.1024632
59 schema:name MicroRNAs define distinct human neuroblastoma cell phenotypes and regulate their differentiation and tumorigenicity
60 schema:pagination 309
61 schema:productId N1397a732d2eb47a2ba91573e962a2bac
62 N2555d0b294384c0ca6dd5341296b4fdd
63 N3433bcbb066f4ab8bdfb8230e8458e73
64 N70420c830a124e748945a1bb58b3d02d
65 N912d8d9b1fea49d99dc87b8ee7d6368b
66 schema:sameAs https://app.dimensions.ai/details/publication/pub.1048033679
67 https://doi.org/10.1186/1471-2407-14-309
68 schema:sdDatePublished 2019-04-10T15:02
69 schema:sdLicense https://scigraph.springernature.com/explorer/license/
70 schema:sdPublisher Nda6780d22d1e4be5b1600a717cc037ba
71 schema:url http://link.springer.com/10.1186%2F1471-2407-14-309
72 sgo:license sg:explorer/license/
73 sgo:sdDataset articles
74 rdf:type schema:ScholarlyArticle
75 N0925dfbdde3249e9a2ee2222b552ecb5 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
76 schema:name Carcinogenesis
77 rdf:type schema:DefinedTerm
78 N1397a732d2eb47a2ba91573e962a2bac schema:name nlm_unique_id
79 schema:value 100967800
80 rdf:type schema:PropertyValue
81 N170585d938b043369aeb1dd147a0bced schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
82 schema:name ELAV-Like Protein 4
83 rdf:type schema:DefinedTerm
84 N21a6a467d7c64b458d4b74143ef5a5f2 rdf:first sg:person.01170011620.41
85 rdf:rest rdf:nil
86 N2555d0b294384c0ca6dd5341296b4fdd schema:name readcube_id
87 schema:value e4d2c2ef509fc2a252b686bcc04af697737c6f416b138344039cc8ca594d5551
88 rdf:type schema:PropertyValue
89 N3166871ed96445848dbccdc3a17a4874 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
90 schema:name Cell Differentiation
91 rdf:type schema:DefinedTerm
92 N316f1b9f42e84fbca72d257bf8a5665a schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
93 schema:name Humans
94 rdf:type schema:DefinedTerm
95 N3433bcbb066f4ab8bdfb8230e8458e73 schema:name doi
96 schema:value 10.1186/1471-2407-14-309
97 rdf:type schema:PropertyValue
98 N447e11a0cac2461481e133bea6beb63e schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
99 schema:name RNA-Binding Proteins
100 rdf:type schema:DefinedTerm
101 N4ffca5c43b6b45aca2719a271f4cf695 rdf:first sg:person.01040304662.31
102 rdf:rest N21a6a467d7c64b458d4b74143ef5a5f2
103 N5a6058343ac048fc92a1cfdd5a04fb85 schema:issueNumber 1
104 rdf:type schema:PublicationIssue
105 N60c5e97921c947679412eee8373d5e65 rdf:first sg:person.0744113216.27
106 rdf:rest N4ffca5c43b6b45aca2719a271f4cf695
107 N60f652801bc244a5802a5caff36e1000 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
108 schema:name Brain Neoplasms
109 rdf:type schema:DefinedTerm
110 N70420c830a124e748945a1bb58b3d02d schema:name pubmed_id
111 schema:value 24885481
112 rdf:type schema:PropertyValue
113 N7f3735433d584ed5a17c3be7d6b66b16 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
114 schema:name Gene Expression Regulation, Neoplastic
115 rdf:type schema:DefinedTerm
116 N912bc41c926142b5963a572785b1764e schema:volumeNumber 14
117 rdf:type schema:PublicationVolume
118 N912d8d9b1fea49d99dc87b8ee7d6368b schema:name dimensions_id
119 schema:value pub.1048033679
120 rdf:type schema:PropertyValue
121 N95120fc9459b44e082d39d0369a44618 rdf:first sg:person.01275212530.13
122 rdf:rest Nf5ce48376b4349178308226a508d767c
123 Nc3da5a59c33d49f29e6570976b0fb793 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
124 schema:name Microarray Analysis
125 rdf:type schema:DefinedTerm
126 Nc7b07b124ea14d67ad1812ddc2f506eb schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
127 schema:name Neural Stem Cells
128 rdf:type schema:DefinedTerm
129 Nda4bc26ba69a465996b0064be07d77c9 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
130 schema:name ELAV Proteins
131 rdf:type schema:DefinedTerm
132 Nda6780d22d1e4be5b1600a717cc037ba schema:name Springer Nature - SN SciGraph project
133 rdf:type schema:Organization
134 Nddab09989668414ba302e94a02e07272 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
135 schema:name Neuroblastoma
136 rdf:type schema:DefinedTerm
137 Ndece3df063804687bbfc1c6282f5fd36 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
138 schema:name Cell Line, Tumor
139 rdf:type schema:DefinedTerm
140 Ne13ec863873c4f888d566b021d8b85cc schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
141 schema:name Child
142 rdf:type schema:DefinedTerm
143 Neacef8cf32684a34ad6850483ec3833e schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
144 schema:name Phenotype
145 rdf:type schema:DefinedTerm
146 Nf5ce48376b4349178308226a508d767c rdf:first sg:person.01104000267.79
147 rdf:rest N60c5e97921c947679412eee8373d5e65
148 Nfb304f51db07484b824ed6d09316f764 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
149 schema:name MicroRNAs
150 rdf:type schema:DefinedTerm
151 anzsrc-for:11 schema:inDefinedTermSet anzsrc-for:
152 schema:name Medical and Health Sciences
153 rdf:type schema:DefinedTerm
154 anzsrc-for:1112 schema:inDefinedTermSet anzsrc-for:
155 schema:name Oncology and Carcinogenesis
156 rdf:type schema:DefinedTerm
157 sg:grant.2473642 http://pending.schema.org/fundedItem sg:pub.10.1186/1471-2407-14-309
158 rdf:type schema:MonetaryGrant
159 sg:journal.1024632 schema:issn 1471-2407
160 schema:name BMC Cancer
161 rdf:type schema:Periodical
162 sg:person.01040304662.31 schema:affiliation https://www.grid.ac/institutes/grid.256023.0
163 schema:familyName Spengler
164 schema:givenName Barbara A
165 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01040304662.31
166 rdf:type schema:Person
167 sg:person.01104000267.79 schema:affiliation https://www.grid.ac/institutes/grid.418185.1
168 schema:familyName Grandinetti
169 schema:givenName Kathryn B
170 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01104000267.79
171 rdf:type schema:Person
172 sg:person.01170011620.41 schema:affiliation https://www.grid.ac/institutes/grid.256023.0
173 schema:familyName Ross
174 schema:givenName Robert A
175 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01170011620.41
176 rdf:type schema:Person
177 sg:person.01275212530.13 schema:affiliation https://www.grid.ac/institutes/grid.251993.5
178 schema:familyName Samaraweera
179 schema:givenName Leleesha
180 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01275212530.13
181 rdf:type schema:Person
182 sg:person.0744113216.27 schema:affiliation https://www.grid.ac/institutes/grid.453554.6
183 schema:familyName Huang
184 schema:givenName Ruojun
185 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0744113216.27
186 rdf:type schema:Person
187 sg:pub.10.1038/313404a0 schema:sameAs https://app.dimensions.ai/details/publication/pub.1051468821
188 https://doi.org/10.1038/313404a0
189 rdf:type schema:CreativeWork
190 sg:pub.10.1038/nm1010-1079 schema:sameAs https://app.dimensions.ai/details/publication/pub.1043279292
191 https://doi.org/10.1038/nm1010-1079
192 rdf:type schema:CreativeWork
193 sg:pub.10.1038/nrn1847 schema:sameAs https://app.dimensions.ai/details/publication/pub.1047057402
194 https://doi.org/10.1038/nrn1847
195 rdf:type schema:CreativeWork
196 sg:pub.10.1038/sj.onc.1209095 schema:sameAs https://app.dimensions.ai/details/publication/pub.1031323858
197 https://doi.org/10.1038/sj.onc.1209095
198 rdf:type schema:CreativeWork
199 https://app.dimensions.ai/details/publication/pub.1083224246 schema:CreativeWork
200 https://doi.org/10.1002/ijc.23153 schema:sameAs https://app.dimensions.ai/details/publication/pub.1033649705
201 rdf:type schema:CreativeWork
202 https://doi.org/10.1002/pbc.24433 schema:sameAs https://app.dimensions.ai/details/publication/pub.1042533154
203 rdf:type schema:CreativeWork
204 https://doi.org/10.1006/dbio.1999.9450 schema:sameAs https://app.dimensions.ai/details/publication/pub.1051936861
205 rdf:type schema:CreativeWork
206 https://doi.org/10.1016/j.semcancer.2006.04.006 schema:sameAs https://app.dimensions.ai/details/publication/pub.1050668481
207 rdf:type schema:CreativeWork
208 https://doi.org/10.1016/j.semcancer.2011.07.001 schema:sameAs https://app.dimensions.ai/details/publication/pub.1028098297
209 rdf:type schema:CreativeWork
210 https://doi.org/10.1056/nejm199910143411601 schema:sameAs https://app.dimensions.ai/details/publication/pub.1017604054
211 rdf:type schema:CreativeWork
212 https://doi.org/10.1073/pnas.0511041103 schema:sameAs https://app.dimensions.ai/details/publication/pub.1046042632
213 rdf:type schema:CreativeWork
214 https://doi.org/10.1073/pnas.83.16.5929 schema:sameAs https://app.dimensions.ai/details/publication/pub.1042712023
215 rdf:type schema:CreativeWork
216 https://doi.org/10.1074/jbc.275.13.9186 schema:sameAs https://app.dimensions.ai/details/publication/pub.1024169911
217 rdf:type schema:CreativeWork
218 https://doi.org/10.1074/jbc.m312663200 schema:sameAs https://app.dimensions.ai/details/publication/pub.1025867111
219 rdf:type schema:CreativeWork
220 https://doi.org/10.1093/carcin/bgs114 schema:sameAs https://app.dimensions.ai/details/publication/pub.1014491814
221 rdf:type schema:CreativeWork
222 https://doi.org/10.1093/jnci/73.2.405 schema:sameAs https://app.dimensions.ai/details/publication/pub.1081843234
223 rdf:type schema:CreativeWork
224 https://doi.org/10.1128/mcb.00316-10 schema:sameAs https://app.dimensions.ai/details/publication/pub.1023616678
225 rdf:type schema:CreativeWork
226 https://doi.org/10.1128/mcb.01694-08 schema:sameAs https://app.dimensions.ai/details/publication/pub.1017449151
227 rdf:type schema:CreativeWork
228 https://doi.org/10.1128/mcb.24.13.5923-5936.2004 schema:sameAs https://app.dimensions.ai/details/publication/pub.1021126403
229 rdf:type schema:CreativeWork
230 https://doi.org/10.1158/0008-5472.can-06-3667 schema:sameAs https://app.dimensions.ai/details/publication/pub.1041483621
231 rdf:type schema:CreativeWork
232 https://doi.org/10.1158/0008-5472.can-10-0970 schema:sameAs https://app.dimensions.ai/details/publication/pub.1044643438
233 rdf:type schema:CreativeWork
234 https://doi.org/10.1371/journal.pone.0005033 schema:sameAs https://app.dimensions.ai/details/publication/pub.1004731588
235 rdf:type schema:CreativeWork
236 https://doi.org/10.1371/journal.pone.0007850 schema:sameAs https://app.dimensions.ai/details/publication/pub.1013228564
237 rdf:type schema:CreativeWork
238 https://doi.org/10.1371/journal.pone.0023461 schema:sameAs https://app.dimensions.ai/details/publication/pub.1050867137
239 rdf:type schema:CreativeWork
240 https://doi.org/10.1517/14728222.2010.510136 schema:sameAs https://app.dimensions.ai/details/publication/pub.1019231404
241 rdf:type schema:CreativeWork
242 https://doi.org/10.1593/neo.04310 schema:sameAs https://app.dimensions.ai/details/publication/pub.1034584550
243 rdf:type schema:CreativeWork
244 https://doi.org/10.1634/stemcells.2005-0441 schema:sameAs https://app.dimensions.ai/details/publication/pub.1048521174
245 rdf:type schema:CreativeWork
246 https://doi.org/10.2174/138161209787315837 schema:sameAs https://app.dimensions.ai/details/publication/pub.1069166847
247 rdf:type schema:CreativeWork
248 https://doi.org/10.4161/cbt.9.6.10894 schema:sameAs https://app.dimensions.ai/details/publication/pub.1072295713
249 rdf:type schema:CreativeWork
250 https://doi.org/10.5772/29142 schema:sameAs https://app.dimensions.ai/details/publication/pub.1047215286
251 rdf:type schema:CreativeWork
252 https://www.grid.ac/institutes/grid.251993.5 schema:alternateName Albert Einstein College of Medicine
253 schema:name Albert Einstein College of Medicine, 1300, Morris Park Ave, 10461, Bronx, NY, USA
254 rdf:type schema:Organization
255 https://www.grid.ac/institutes/grid.256023.0 schema:alternateName Fordham University
256 schema:name Fordham University, 441 E. Fordham Road, 10458, Bronx, NY, USA
257 rdf:type schema:Organization
258 https://www.grid.ac/institutes/grid.418185.1 schema:alternateName Genomics Institute of the Novartis Research Foundation
259 schema:name Genomics Institute of the Novartis Research Foundation, San Diego, CA, USA
260 rdf:type schema:Organization
261 https://www.grid.ac/institutes/grid.453554.6 schema:alternateName Consolidated Edison (United States)
262 schema:name Edison, NJ, USA
263 rdf:type schema:Organization
 




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


...