miR-514a regulates the tumour suppressor NF1 and modulates BRAFi sensitivity in melanoma
Identifieur interne : 002626 ( Main/Exploration ); précédent : 002625; suivant : 002627miR-514a regulates the tumour suppressor NF1 and modulates BRAFi sensitivity in melanoma
Auteurs : Mitchell S. Stark [Australie] ; Vanessa F. Bonazzi [France] ; Glen M. Boyle [Australie] ; Jane M. Palmer [Australie] ; Judith Symmons [Australie] ; Catherine M. Lanagan [Australie] ; Christopher W. Schmidt [Australie] ; Adrian C. Herington [Australie] ; Robert Ballotti [France] ; Pamela M. Pollock [Australie] ; Nicholas K. Hayward [Australie]Source :
- Oncotarget [ 1949-2553 ] ; 2015.
Descripteurs français
- KwdFr :
- Analyse de profil d'expression de gènes, Antinéoplasiques (pharmacologie), Gènes suppresseurs de tumeur, Humains, Indoles (pharmacologie), Lignée cellulaire tumorale, Mutagenèse dirigée, Mélanome (anatomopathologie), Mélanome (génétique), Mélanome (métabolisme), Neurofibromine-1 (biosynthèse), Neurofibromine-1 (génétique), Protéines proto-oncogènes B-raf (métabolisme), Réaction de polymérisation en chaîne, Régulation de l'expression des gènes tumoraux (génétique), Sulfonamides (pharmacologie), Séquençage par oligonucléotides en batterie, Technique de Western, Transfection, microARN (génétique).
- MESH :
- anatomopathologie : Mélanome.
- biosynthèse : Neurofibromine-1.
- génétique : Mélanome, Neurofibromine-1, Régulation de l'expression des gènes tumoraux, microARN.
- métabolisme : Mélanome, Protéines proto-oncogènes B-raf.
- pharmacologie : Antinéoplasiques, Indoles, Sulfonamides.
- Analyse de profil d'expression de gènes, Gènes suppresseurs de tumeur, Humains, Lignée cellulaire tumorale, Mutagenèse dirigée, Réaction de polymérisation en chaîne, Séquençage par oligonucléotides en batterie, Technique de Western, Transfection.
English descriptors
- KwdEn :
- Antineoplastic Agents (pharmacology), Blotting, Western, Cell Line, Tumor, Gene Expression Profiling, Gene Expression Regulation, Neoplastic (genetics), Genes, Tumor Suppressor, Humans, Indoles (pharmacology), Melanoma (genetics), Melanoma (metabolism), Melanoma (pathology), MicroRNAs (genetics), Mutagenesis, Site-Directed, Neurofibromin 1 (biosynthesis), Neurofibromin 1 (genetics), Oligonucleotide Array Sequence Analysis, Polymerase Chain Reaction, Proto-Oncogene Proteins B-raf (metabolism), Sulfonamides (pharmacology), Transfection.
- MESH :
- chemical , biosynthesis : Neurofibromin 1.
- chemical , genetics : MicroRNAs, Neurofibromin 1.
- chemical , metabolism : Proto-Oncogene Proteins B-raf.
- chemical , pharmacology : Antineoplastic Agents, Indoles, Sulfonamides.
- genetics : Gene Expression Regulation, Neoplastic, Melanoma.
- metabolism : Melanoma.
- pathology : Melanoma.
- Blotting, Western, Cell Line, Tumor, Gene Expression Profiling, Genes, Tumor Suppressor, Humans, Mutagenesis, Site-Directed, Oligonucleotide Array Sequence Analysis, Polymerase Chain Reaction, Transfection.
Abstract
To identify ‘melanoma-specific’ microRNAs (miRNAs) we used an unbiased microRNA profiling approach to comprehensively study cutaneous melanoma in relation to other solid malignancies, which revealed 233 differentially expressed (≥2 fold, p < 0.05) miRNAs. Among the top 20 most significantly different miRNAs was hsa-miR-514a-3p. miR-514a is a member of a cluster of miRNAs (miR-506-514) involved in initiating melanocyte transformation and promotion of melanoma growth. We found miR-514a was expressed in 38/55 (69%) melanoma cell lines but in only 1/34 (3%) other solid cancers. To identify miR-514a regulated targets we conducted a miR-514a-mRNA ‘pull-down’ experiment, which revealed hundreds of genes, including:
Url:
PubMed: 25980496
PubMed Central: 4627343
Affiliations:
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Stark</name><affiliation wicri:level="1"><nlm:aff id="A1"> QIMR Berghofer Medical Research Institute, Herston, Brisbane, QLD, Australia</nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea> QIMR Berghofer Medical Research Institute, Herston, Brisbane, QLD</wicri:regionArea><wicri:noRegion>QLD</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="A2"> School of Biomedical Sciences, Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Australia</nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea> School of Biomedical Sciences, Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane</wicri:regionArea><wicri:noRegion>Brisbane</wicri:noRegion></affiliation></author><author><name sortKey="Bonazzi, Vanessa F" sort="Bonazzi, Vanessa F" uniqKey="Bonazzi V" first="Vanessa F." last="Bonazzi">Vanessa F. 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Stark</name><affiliation wicri:level="1"><nlm:aff id="A1"> QIMR Berghofer Medical Research Institute, Herston, Brisbane, QLD, Australia</nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea> QIMR Berghofer Medical Research Institute, Herston, Brisbane, QLD</wicri:regionArea><wicri:noRegion>QLD</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="A2"> School of Biomedical Sciences, Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Australia</nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea> School of Biomedical Sciences, Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane</wicri:regionArea><wicri:noRegion>Brisbane</wicri:noRegion></affiliation></author><author><name sortKey="Bonazzi, Vanessa F" sort="Bonazzi, Vanessa F" uniqKey="Bonazzi V" first="Vanessa F." last="Bonazzi">Vanessa F. Bonazzi</name><affiliation wicri:level="3"><nlm:aff id="A3"> Inserm U1065, Centre Méditerranéen de Médecine Moléculaire, Equipe 1, Biologie et pathologies des mélanocytes, Nice, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea> Inserm U1065, Centre Méditerranéen de Médecine Moléculaire, Equipe 1, Biologie et pathologies des mélanocytes, Nice</wicri:regionArea><placeName><region type="region">Provence-Alpes-Côte d'Azur</region><region type="old region">Provence-Alpes-Côte d'Azur</region><settlement type="city">Nice</settlement></placeName></affiliation></author><author><name sortKey="Boyle, Glen M" sort="Boyle, Glen M" uniqKey="Boyle G" first="Glen M." last="Boyle">Glen M. Boyle</name><affiliation wicri:level="1"><nlm:aff id="A1"> QIMR Berghofer Medical Research Institute, Herston, Brisbane, QLD, Australia</nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea> QIMR Berghofer Medical Research Institute, Herston, Brisbane, QLD</wicri:regionArea><wicri:noRegion>QLD</wicri:noRegion></affiliation></author><author><name sortKey="Palmer, Jane M" sort="Palmer, Jane M" uniqKey="Palmer J" first="Jane M." last="Palmer">Jane M. Palmer</name><affiliation wicri:level="1"><nlm:aff id="A1"> QIMR Berghofer Medical Research Institute, Herston, Brisbane, QLD, Australia</nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea> QIMR Berghofer Medical Research Institute, Herston, Brisbane, QLD</wicri:regionArea><wicri:noRegion>QLD</wicri:noRegion></affiliation></author><author><name sortKey="Symmons, Judith" sort="Symmons, Judith" uniqKey="Symmons J" first="Judith" last="Symmons">Judith Symmons</name><affiliation wicri:level="1"><nlm:aff id="A1"> QIMR Berghofer Medical Research Institute, Herston, Brisbane, QLD, Australia</nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea> QIMR Berghofer Medical Research Institute, Herston, Brisbane, QLD</wicri:regionArea><wicri:noRegion>QLD</wicri:noRegion></affiliation></author><author><name sortKey="Lanagan, Catherine M" sort="Lanagan, Catherine M" uniqKey="Lanagan C" first="Catherine M." last="Lanagan">Catherine M. Lanagan</name><affiliation wicri:level="1"><nlm:aff id="A1"> QIMR Berghofer Medical Research Institute, Herston, Brisbane, QLD, Australia</nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea> QIMR Berghofer Medical Research Institute, Herston, Brisbane, QLD</wicri:regionArea><wicri:noRegion>QLD</wicri:noRegion></affiliation></author><author><name sortKey="Schmidt, Christopher W" sort="Schmidt, Christopher W" uniqKey="Schmidt C" first="Christopher W." last="Schmidt">Christopher W. Schmidt</name><affiliation wicri:level="1"><nlm:aff id="A1"> QIMR Berghofer Medical Research Institute, Herston, Brisbane, QLD, Australia</nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea> QIMR Berghofer Medical Research Institute, Herston, Brisbane, QLD</wicri:regionArea><wicri:noRegion>QLD</wicri:noRegion></affiliation></author><author><name sortKey="Herington, Adrian C" sort="Herington, Adrian C" uniqKey="Herington A" first="Adrian C." last="Herington">Adrian C. Herington</name><affiliation wicri:level="1"><nlm:aff id="A2"> School of Biomedical Sciences, Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Australia</nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea> School of Biomedical Sciences, Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane</wicri:regionArea><wicri:noRegion>Brisbane</wicri:noRegion></affiliation></author><author><name sortKey="Ballotti, Robert" sort="Ballotti, Robert" uniqKey="Ballotti R" first="Robert" last="Ballotti">Robert Ballotti</name><affiliation wicri:level="3"><nlm:aff id="A3"> Inserm U1065, Centre Méditerranéen de Médecine Moléculaire, Equipe 1, Biologie et pathologies des mélanocytes, Nice, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea> Inserm U1065, Centre Méditerranéen de Médecine Moléculaire, Equipe 1, Biologie et pathologies des mélanocytes, Nice</wicri:regionArea><placeName><region type="region">Provence-Alpes-Côte d'Azur</region><region type="old region">Provence-Alpes-Côte d'Azur</region><settlement type="city">Nice</settlement></placeName></affiliation></author><author><name sortKey="Pollock, Pamela M" sort="Pollock, Pamela M" uniqKey="Pollock P" first="Pamela M." last="Pollock">Pamela M. Pollock</name><affiliation wicri:level="1"><nlm:aff id="A2"> School of Biomedical Sciences, Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Australia</nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea> School of Biomedical Sciences, Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane</wicri:regionArea><wicri:noRegion>Brisbane</wicri:noRegion></affiliation></author><author><name sortKey="Hayward, Nicholas K" sort="Hayward, Nicholas K" uniqKey="Hayward N" first="Nicholas K." last="Hayward">Nicholas K. Hayward</name><affiliation wicri:level="1"><nlm:aff id="A1"> QIMR Berghofer Medical Research Institute, Herston, Brisbane, QLD, Australia</nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea> QIMR Berghofer Medical Research Institute, Herston, Brisbane, QLD</wicri:regionArea><wicri:noRegion>QLD</wicri:noRegion></affiliation></author></analytic><series><title level="j">Oncotarget</title><idno type="eISSN">1949-2553</idno><imprint><date when="2015">2015</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Antineoplastic Agents (pharmacology)</term><term>Blotting, Western</term><term>Cell Line, Tumor</term><term>Gene Expression Profiling</term><term>Gene Expression Regulation, Neoplastic (genetics)</term><term>Genes, Tumor Suppressor</term><term>Humans</term><term>Indoles (pharmacology)</term><term>Melanoma (genetics)</term><term>Melanoma (metabolism)</term><term>Melanoma (pathology)</term><term>MicroRNAs (genetics)</term><term>Mutagenesis, Site-Directed</term><term>Neurofibromin 1 (biosynthesis)</term><term>Neurofibromin 1 (genetics)</term><term>Oligonucleotide Array Sequence Analysis</term><term>Polymerase Chain Reaction</term><term>Proto-Oncogene Proteins B-raf (metabolism)</term><term>Sulfonamides (pharmacology)</term><term>Transfection</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Analyse de profil d'expression de gènes</term><term>Antinéoplasiques (pharmacologie)</term><term>Gènes suppresseurs de tumeur</term><term>Humains</term><term>Indoles (pharmacologie)</term><term>Lignée cellulaire tumorale</term><term>Mutagenèse dirigée</term><term>Mélanome (anatomopathologie)</term><term>Mélanome (génétique)</term><term>Mélanome (métabolisme)</term><term>Neurofibromine-1 (biosynthèse)</term><term>Neurofibromine-1 (génétique)</term><term>Protéines proto-oncogènes B-raf (métabolisme)</term><term>Réaction de polymérisation en chaîne</term><term>Régulation de l'expression des gènes tumoraux (génétique)</term><term>Sulfonamides (pharmacologie)</term><term>Séquençage par oligonucléotides en batterie</term><term>Technique de Western</term><term>Transfection</term><term>microARN (génétique)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="biosynthesis" xml:lang="en"><term>Neurofibromin 1</term></keywords><keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>MicroRNAs</term><term>Neurofibromin 1</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Proto-Oncogene Proteins B-raf</term></keywords><keywords scheme="MESH" type="chemical" qualifier="pharmacology" xml:lang="en"><term>Antineoplastic Agents</term><term>Indoles</term><term>Sulfonamides</term></keywords><keywords scheme="MESH" qualifier="anatomopathologie" xml:lang="fr"><term>Mélanome</term></keywords><keywords scheme="MESH" qualifier="biosynthèse" xml:lang="fr"><term>Neurofibromine-1</term></keywords><keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Gene Expression Regulation, Neoplastic</term><term>Melanoma</term></keywords><keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>Mélanome</term><term>Neurofibromine-1</term><term>Régulation de l'expression des gènes tumoraux</term><term>microARN</term></keywords><keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>Melanoma</term></keywords><keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Mélanome</term><term>Protéines proto-oncogènes B-raf</term></keywords><keywords scheme="MESH" qualifier="pathology" xml:lang="en"><term>Melanoma</term></keywords><keywords scheme="MESH" qualifier="pharmacologie" xml:lang="fr"><term>Antinéoplasiques</term><term>Indoles</term><term>Sulfonamides</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Blotting, Western</term><term>Cell Line, Tumor</term><term>Gene Expression Profiling</term><term>Genes, Tumor Suppressor</term><term>Humans</term><term>Mutagenesis, Site-Directed</term><term>Oligonucleotide Array Sequence Analysis</term><term>Polymerase Chain Reaction</term><term>Transfection</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Analyse de profil d'expression de gènes</term><term>Gènes suppresseurs de tumeur</term><term>Humains</term><term>Lignée cellulaire tumorale</term><term>Mutagenèse dirigée</term><term>Réaction de polymérisation en chaîne</term><term>Séquençage par oligonucléotides en batterie</term><term>Technique de Western</term><term>Transfection</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>To identify ‘melanoma-specific’ microRNAs (miRNAs) we used an unbiased microRNA profiling approach to comprehensively study cutaneous melanoma in relation to other solid malignancies, which revealed 233 differentially expressed (≥2 fold, p < 0.05) miRNAs. Among the top 20 most significantly different miRNAs was hsa-miR-514a-3p. miR-514a is a member of a cluster of miRNAs (miR-506-514) involved in initiating melanocyte transformation and promotion of melanoma growth. We found miR-514a was expressed in 38/55 (69%) melanoma cell lines but in only 1/34 (3%) other solid cancers. To identify miR-514a regulated targets we conducted a miR-514a-mRNA ‘pull-down’ experiment, which revealed hundreds of genes, including: <italic>CTNNB1</italic>, <italic>CDK2</italic>, <italic>MC1R</italic>, and <italic>NF1</italic>, previously associated with melanoma. <italic>NF1</italic> was selected for functional validation because of its recent implication in acquired resistance to <italic>BRAFV600E</italic>-targeted therapy. Luciferase-reporter assays confirmed <italic>NF1</italic> as a direct target of miR-514a and over-expression of miR-514a in melanoma cell lines inhibited NF1 expression, which correlated with increased survival of <italic>BRAFV600E</italic> cells treated with PLX4032. These data provide another mechanism for the dysregulation of the MAPK pathway which may contribute to the profound resistance associated with current RAF-targeted therapies.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Hanahan, D" uniqKey="Hanahan D">D Hanahan</name></author><author><name sortKey="Weinberg, Ra" uniqKey="Weinberg R">RA Weinberg</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Bonazzi, Vf" uniqKey="Bonazzi V">VF Bonazzi</name></author><author><name sortKey="Stark, Ms" uniqKey="Stark M">MS Stark</name></author><author><name sortKey="Hayward, Nk" uniqKey="Hayward N">NK Hayward</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Gaur, A" uniqKey="Gaur A">A Gaur</name></author><author><name sortKey="Jewell, Da" uniqKey="Jewell D">DA Jewell</name></author><author><name sortKey="Liang, Y" uniqKey="Liang Y">Y Liang</name></author><author><name 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L">LM Liau</name></author><author><name sortKey="Cloughesy, Tf" uniqKey="Cloughesy T">TF Cloughesy</name></author><author><name sortKey="Mischel, Ps" uniqKey="Mischel P">PS Mischel</name></author><author><name sortKey="Parret, A" uniqKey="Parret A">A Parret</name></author><author><name sortKey="Seiler, J" uniqKey="Seiler J">J Seiler</name></author><author><name sortKey="Moldenhauer, G" uniqKey="Moldenhauer G">G Moldenhauer</name></author><author><name sortKey="Scheffzek, K" uniqKey="Scheffzek K">K Scheffzek</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Hollstein, Pe" uniqKey="Hollstein P">PE Hollstein</name></author><author><name sortKey="Cichowski, K" uniqKey="Cichowski K">K Cichowski</name></author></analytic></biblStruct></listBibl></div1></back></TEI><affiliations><list><country><li>Australie</li><li>France</li></country><region><li>Provence-Alpes-Côte d'Azur</li></region><settlement><li>Nice</li></settlement></list><tree><country name="Australie"><noRegion><name sortKey="Stark, Mitchell S" sort="Stark, Mitchell S" uniqKey="Stark M" first="Mitchell S." last="Stark">Mitchell S. Stark</name></noRegion><name sortKey="Boyle, Glen M" sort="Boyle, Glen M" uniqKey="Boyle G" first="Glen M." last="Boyle">Glen M. Boyle</name><name sortKey="Hayward, Nicholas K" sort="Hayward, Nicholas K" uniqKey="Hayward N" first="Nicholas K." last="Hayward">Nicholas K. Hayward</name><name sortKey="Herington, Adrian C" sort="Herington, Adrian C" uniqKey="Herington A" first="Adrian C." last="Herington">Adrian C. Herington</name><name sortKey="Lanagan, Catherine M" sort="Lanagan, Catherine M" uniqKey="Lanagan C" first="Catherine M." last="Lanagan">Catherine M. Lanagan</name><name sortKey="Palmer, Jane M" sort="Palmer, Jane M" uniqKey="Palmer J" first="Jane M." last="Palmer">Jane M. Palmer</name><name sortKey="Pollock, Pamela M" sort="Pollock, Pamela M" uniqKey="Pollock P" first="Pamela M." last="Pollock">Pamela M. Pollock</name><name sortKey="Schmidt, Christopher W" sort="Schmidt, Christopher W" uniqKey="Schmidt C" first="Christopher W." last="Schmidt">Christopher W. Schmidt</name><name sortKey="Stark, Mitchell S" sort="Stark, Mitchell S" uniqKey="Stark M" first="Mitchell S." last="Stark">Mitchell S. Stark</name><name sortKey="Symmons, Judith" sort="Symmons, Judith" uniqKey="Symmons J" first="Judith" last="Symmons">Judith Symmons</name></country><country name="France"><region name="Provence-Alpes-Côte d'Azur"><name sortKey="Bonazzi, Vanessa F" sort="Bonazzi, Vanessa F" uniqKey="Bonazzi V" first="Vanessa F." last="Bonazzi">Vanessa F. Bonazzi</name></region><name sortKey="Ballotti, Robert" sort="Ballotti, Robert" uniqKey="Ballotti R" first="Robert" last="Ballotti">Robert Ballotti</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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