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MicroRNA-193b-3p acts as a tumor suppressor by targeting the MYB oncogene in T-cell acute lymphoblastic leukemia
The MYB oncogene is a leucine zipper transcription factor essential for normal and malignant hematopoiesis. In T-cell acute lymphoblastic leukemia (T-ALL), elevated MYB levels can arise directly through T-cell receptor-mediated MYB translocations, genomic MYB duplications or enhanced TAL1 complex bi...
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| Published in: | Leukemia 2015-04, Vol.29 (4), p.798-806 |
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| container_title | Leukemia |
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| creator | Mets, E Van der Meulen, J Van Peer, G Boice, M Mestdagh, P Van de Walle, I Lammens, T Goossens, S De Moerloose, B Benoit, Y Van Roy, N Clappier, E Poppe, B Vandesompele, J Wendel, H-G Taghon, T Rondou, P Soulier, J Van Vlierberghe, P Speleman, F |
| description | The MYB oncogene is a leucine zipper transcription factor essential for normal and malignant hematopoiesis. In T-cell acute lymphoblastic leukemia (T-ALL), elevated MYB levels can arise directly through T-cell receptor-mediated MYB translocations, genomic MYB duplications or enhanced TAL1 complex binding at the MYB locus or indirectly through the TAL1/miR-223/FBXW7 regulatory axis. In this study, we used an unbiased MYB 3'untranslated region-microRNA (miRNA) library screen and identified 33 putative MYB-targeting miRNAs. Subsequently, transcriptome data from two independent T-ALL cohorts and different subsets of normal T-cells were used to select miRNAs with relevance in the context of normal and malignant T-cell transformation. Hereby, miR-193b-3p was identified as a novel bona fide tumor-suppressor miRNA that targets MYB during malignant T-cell transformation thereby offering an entry point for efficient MYB targeting-oriented therapies for human T-ALL. |
| doi_str_mv | 10.1038/leu.2014.276 |
| format | article |
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In T-cell acute lymphoblastic leukemia (T-ALL), elevated MYB levels can arise directly through T-cell receptor-mediated MYB translocations, genomic MYB duplications or enhanced TAL1 complex binding at the MYB locus or indirectly through the TAL1/miR-223/FBXW7 regulatory axis. In this study, we used an unbiased MYB 3'untranslated region-microRNA (miRNA) library screen and identified 33 putative MYB-targeting miRNAs. Subsequently, transcriptome data from two independent T-ALL cohorts and different subsets of normal T-cells were used to select miRNAs with relevance in the context of normal and malignant T-cell transformation. Hereby, miR-193b-3p was identified as a novel bona fide tumor-suppressor miRNA that targets MYB during malignant T-cell transformation thereby offering an entry point for efficient MYB targeting-oriented therapies for human T-ALL.</description><identifier>ISSN: 0887-6924</identifier><identifier>EISSN: 1476-5551</identifier><identifier>DOI: 10.1038/leu.2014.276</identifier><identifier>PMID: 25231743</identifier><language>eng</language><publisher>England: Nature Publishing Group</publisher><subject>3' Untranslated Regions ; Acute lymphoblastic leukemia ; Acute lymphocytic leukemia ; Animals ; Basic Helix-Loop-Helix Transcription Factors - genetics ; Basic Helix-Loop-Helix Transcription Factors - metabolism ; Care and treatment ; Cdc4 protein ; Cell Cycle Proteins - genetics ; Cell Cycle Proteins - metabolism ; Cell Transformation, Neoplastic - genetics ; Cell Transformation, Neoplastic - metabolism ; Development and progression ; F-Box Proteins - genetics ; F-Box Proteins - metabolism ; F-Box-WD Repeat-Containing Protein 7 ; Gene expression ; Gene Expression Profiling ; Gene Expression Regulation, Leukemic ; Genetic aspects ; Genomic Library ; Health aspects ; Hematopoiesis ; Humans ; Innovations ; Leucine ; Leucine zipper proteins ; Leukemia ; Lymphatic leukemia ; Lymphocytes T ; Mice ; MicroRNA ; MicroRNAs ; MicroRNAs - genetics ; MicroRNAs - metabolism ; miRNA ; Molecular targeted therapy ; Oncogenes ; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma - genetics ; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma - metabolism ; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma - pathology ; Primary Cell Culture ; Proto-Oncogene Proteins - genetics ; Proto-Oncogene Proteins - metabolism ; Proto-Oncogene Proteins c-myb - genetics ; Proto-Oncogene Proteins c-myb - metabolism ; Ribonucleic acid ; RNA ; Signal Transduction ; T cell receptors ; T-Cell Acute Lymphocytic Leukemia Protein 1 ; T-Lymphocytes - metabolism ; T-Lymphocytes - pathology ; Transcriptome ; Transformations ; Translocation ; Tumor suppressor genes ; Tumors ; Ubiquitin-Protein Ligases - genetics ; Ubiquitin-Protein Ligases - metabolism</subject><ispartof>Leukemia, 2015-04, Vol.29 (4), p.798-806</ispartof><rights>COPYRIGHT 2015 Nature Publishing Group</rights><rights>Copyright Nature Publishing Group Apr 2015</rights><rights>Macmillan Publishers Limited 2015.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c602t-c6717f4c95c5852059085f7362b49383b98a52ea73b7faf6d4cb5bedf8e40af33</citedby><cites>FETCH-LOGICAL-c602t-c6717f4c95c5852059085f7362b49383b98a52ea73b7faf6d4cb5bedf8e40af33</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,315,786,790,891,27957,27958</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25231743$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Mets, E</creatorcontrib><creatorcontrib>Van der Meulen, J</creatorcontrib><creatorcontrib>Van Peer, G</creatorcontrib><creatorcontrib>Boice, M</creatorcontrib><creatorcontrib>Mestdagh, P</creatorcontrib><creatorcontrib>Van de Walle, I</creatorcontrib><creatorcontrib>Lammens, T</creatorcontrib><creatorcontrib>Goossens, S</creatorcontrib><creatorcontrib>De Moerloose, B</creatorcontrib><creatorcontrib>Benoit, Y</creatorcontrib><creatorcontrib>Van Roy, N</creatorcontrib><creatorcontrib>Clappier, E</creatorcontrib><creatorcontrib>Poppe, B</creatorcontrib><creatorcontrib>Vandesompele, J</creatorcontrib><creatorcontrib>Wendel, H-G</creatorcontrib><creatorcontrib>Taghon, T</creatorcontrib><creatorcontrib>Rondou, P</creatorcontrib><creatorcontrib>Soulier, J</creatorcontrib><creatorcontrib>Van Vlierberghe, P</creatorcontrib><creatorcontrib>Speleman, F</creatorcontrib><title>MicroRNA-193b-3p acts as a tumor suppressor by targeting the MYB oncogene in T-cell acute lymphoblastic leukemia</title><title>Leukemia</title><addtitle>Leukemia</addtitle><description>The MYB oncogene is a leucine zipper transcription factor essential for normal and malignant hematopoiesis. In T-cell acute lymphoblastic leukemia (T-ALL), elevated MYB levels can arise directly through T-cell receptor-mediated MYB translocations, genomic MYB duplications or enhanced TAL1 complex binding at the MYB locus or indirectly through the TAL1/miR-223/FBXW7 regulatory axis. In this study, we used an unbiased MYB 3'untranslated region-microRNA (miRNA) library screen and identified 33 putative MYB-targeting miRNAs. Subsequently, transcriptome data from two independent T-ALL cohorts and different subsets of normal T-cells were used to select miRNAs with relevance in the context of normal and malignant T-cell transformation. Hereby, miR-193b-3p was identified as a novel bona fide tumor-suppressor miRNA that targets MYB during malignant T-cell transformation thereby offering an entry point for efficient MYB targeting-oriented therapies for human T-ALL.</description><subject>3' Untranslated Regions</subject><subject>Acute lymphoblastic leukemia</subject><subject>Acute lymphocytic leukemia</subject><subject>Animals</subject><subject>Basic Helix-Loop-Helix Transcription Factors - genetics</subject><subject>Basic Helix-Loop-Helix Transcription Factors - metabolism</subject><subject>Care and treatment</subject><subject>Cdc4 protein</subject><subject>Cell Cycle Proteins - genetics</subject><subject>Cell Cycle Proteins - metabolism</subject><subject>Cell Transformation, Neoplastic - genetics</subject><subject>Cell Transformation, Neoplastic - metabolism</subject><subject>Development and progression</subject><subject>F-Box Proteins - genetics</subject><subject>F-Box Proteins - metabolism</subject><subject>F-Box-WD Repeat-Containing Protein 7</subject><subject>Gene expression</subject><subject>Gene Expression Profiling</subject><subject>Gene Expression Regulation, Leukemic</subject><subject>Genetic aspects</subject><subject>Genomic Library</subject><subject>Health aspects</subject><subject>Hematopoiesis</subject><subject>Humans</subject><subject>Innovations</subject><subject>Leucine</subject><subject>Leucine zipper proteins</subject><subject>Leukemia</subject><subject>Lymphatic leukemia</subject><subject>Lymphocytes T</subject><subject>Mice</subject><subject>MicroRNA</subject><subject>MicroRNAs</subject><subject>MicroRNAs - genetics</subject><subject>MicroRNAs - metabolism</subject><subject>miRNA</subject><subject>Molecular targeted therapy</subject><subject>Oncogenes</subject><subject>Precursor T-Cell Lymphoblastic Leukemia-Lymphoma - genetics</subject><subject>Precursor T-Cell Lymphoblastic Leukemia-Lymphoma - metabolism</subject><subject>Precursor T-Cell Lymphoblastic Leukemia-Lymphoma - pathology</subject><subject>Primary Cell Culture</subject><subject>Proto-Oncogene Proteins - genetics</subject><subject>Proto-Oncogene Proteins - metabolism</subject><subject>Proto-Oncogene Proteins c-myb - genetics</subject><subject>Proto-Oncogene Proteins c-myb - metabolism</subject><subject>Ribonucleic acid</subject><subject>RNA</subject><subject>Signal Transduction</subject><subject>T cell receptors</subject><subject>T-Cell Acute Lymphocytic Leukemia Protein 1</subject><subject>T-Lymphocytes - metabolism</subject><subject>T-Lymphocytes - pathology</subject><subject>Transcriptome</subject><subject>Transformations</subject><subject>Translocation</subject><subject>Tumor suppressor genes</subject><subject>Tumors</subject><subject>Ubiquitin-Protein Ligases - genetics</subject><subject>Ubiquitin-Protein Ligases - metabolism</subject><issn>0887-6924</issn><issn>1476-5551</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><recordid>eNqFkl1rFDEUhgdR7LZ657UEBPHCWfOdzI2wFr-gVZB64VXIZM_sps4k4yQj7L9vlta6FVESkpA8eXNOzltVTwheEsz0qx7mJcWEL6mS96oF4UrWQghyv1pgrVUtG8qPquOULjHeH8qH1REVlBHF2aIaz72b4pdPq5o0rK3ZiKzLCdnSUZ6HOKE0j-MEKZVlu0PZThvIPmxQ3gI6__YGxeDiBgIgH9BF7aDvi8ScAfW7YdzGtrcpe4dKmN9h8PZR9aCzfYLHN_NJ9fXd24vTD_XZ5_cfT1dntZOY5jIqojruGuGEFhSLBmvRKSZpyxumWdtoKyhYxVrV2U6uuWtFC-tOA8e2Y-yken2tO87tAGsHIU-2N-PkBzvtTLTe3D0Jfms28afhusGS0yLw4kZgij9mSNkMPu3TswHinAyRmjHBCcUFffYHehnnKZT0DGWMSMJwI_5FEakoVlQp9Zva2B6MD10s0bn902bFCW4wp40u1PIvVGnr8scuBuh82b9z4fnBhS3YPm9T7OfsY0hmJQkueWhM_gceKr68Bot_Upqgu_1bgs3emaaU3OydaYozC_70sB638C8rsismxtqn</recordid><startdate>20150401</startdate><enddate>20150401</enddate><creator>Mets, E</creator><creator>Van der Meulen, J</creator><creator>Van Peer, G</creator><creator>Boice, M</creator><creator>Mestdagh, 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acts as a tumor suppressor by targeting the MYB oncogene in T-cell acute lymphoblastic leukemia</title><author>Mets, E ; Van der Meulen, J ; Van Peer, G ; Boice, M ; Mestdagh, P ; Van de Walle, I ; Lammens, T ; Goossens, S ; De Moerloose, B ; Benoit, Y ; Van Roy, N ; Clappier, E ; Poppe, B ; Vandesompele, J ; Wendel, H-G ; Taghon, T ; Rondou, P ; Soulier, J ; Van Vlierberghe, P ; Speleman, F</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c602t-c6717f4c95c5852059085f7362b49383b98a52ea73b7faf6d4cb5bedf8e40af33</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>3' Untranslated Regions</topic><topic>Acute lymphoblastic leukemia</topic><topic>Acute lymphocytic leukemia</topic><topic>Animals</topic><topic>Basic Helix-Loop-Helix Transcription Factors - genetics</topic><topic>Basic Helix-Loop-Helix Transcription Factors - metabolism</topic><topic>Care and treatment</topic><topic>Cdc4 protein</topic><topic>Cell Cycle Proteins - genetics</topic><topic>Cell Cycle Proteins - metabolism</topic><topic>Cell Transformation, Neoplastic - genetics</topic><topic>Cell Transformation, Neoplastic - metabolism</topic><topic>Development and progression</topic><topic>F-Box Proteins - genetics</topic><topic>F-Box Proteins - metabolism</topic><topic>F-Box-WD Repeat-Containing Protein 7</topic><topic>Gene expression</topic><topic>Gene Expression Profiling</topic><topic>Gene Expression Regulation, Leukemic</topic><topic>Genetic aspects</topic><topic>Genomic Library</topic><topic>Health aspects</topic><topic>Hematopoiesis</topic><topic>Humans</topic><topic>Innovations</topic><topic>Leucine</topic><topic>Leucine zipper proteins</topic><topic>Leukemia</topic><topic>Lymphatic leukemia</topic><topic>Lymphocytes T</topic><topic>Mice</topic><topic>MicroRNA</topic><topic>MicroRNAs</topic><topic>MicroRNAs - genetics</topic><topic>MicroRNAs - metabolism</topic><topic>miRNA</topic><topic>Molecular targeted therapy</topic><topic>Oncogenes</topic><topic>Precursor T-Cell Lymphoblastic Leukemia-Lymphoma - genetics</topic><topic>Precursor T-Cell Lymphoblastic Leukemia-Lymphoma - metabolism</topic><topic>Precursor T-Cell Lymphoblastic Leukemia-Lymphoma - pathology</topic><topic>Primary Cell Culture</topic><topic>Proto-Oncogene Proteins - genetics</topic><topic>Proto-Oncogene Proteins - metabolism</topic><topic>Proto-Oncogene Proteins c-myb - genetics</topic><topic>Proto-Oncogene Proteins c-myb - metabolism</topic><topic>Ribonucleic acid</topic><topic>RNA</topic><topic>Signal Transduction</topic><topic>T cell receptors</topic><topic>T-Cell Acute Lymphocytic Leukemia Protein 1</topic><topic>T-Lymphocytes - metabolism</topic><topic>T-Lymphocytes - pathology</topic><topic>Transcriptome</topic><topic>Transformations</topic><topic>Translocation</topic><topic>Tumor suppressor genes</topic><topic>Tumors</topic><topic>Ubiquitin-Protein 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leukemia</atitle><jtitle>Leukemia</jtitle><addtitle>Leukemia</addtitle><date>2015-04-01</date><risdate>2015</risdate><volume>29</volume><issue>4</issue><spage>798</spage><epage>806</epage><pages>798-806</pages><issn>0887-6924</issn><eissn>1476-5551</eissn><notes>ObjectType-Article-1</notes><notes>SourceType-Scholarly Journals-1</notes><notes>ObjectType-Feature-2</notes><notes>content type line 23</notes><notes>These two authors shared co-authorship.</notes><abstract>The MYB oncogene is a leucine zipper transcription factor essential for normal and malignant hematopoiesis. In T-cell acute lymphoblastic leukemia (T-ALL), elevated MYB levels can arise directly through T-cell receptor-mediated MYB translocations, genomic MYB duplications or enhanced TAL1 complex binding at the MYB locus or indirectly through the TAL1/miR-223/FBXW7 regulatory axis. In this study, we used an unbiased MYB 3'untranslated region-microRNA (miRNA) library screen and identified 33 putative MYB-targeting miRNAs. Subsequently, transcriptome data from two independent T-ALL cohorts and different subsets of normal T-cells were used to select miRNAs with relevance in the context of normal and malignant T-cell transformation. Hereby, miR-193b-3p was identified as a novel bona fide tumor-suppressor miRNA that targets MYB during malignant T-cell transformation thereby offering an entry point for efficient MYB targeting-oriented therapies for human T-ALL.</abstract><cop>England</cop><pub>Nature Publishing Group</pub><pmid>25231743</pmid><doi>10.1038/leu.2014.276</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Leukemia, 2015-04, Vol.29 (4), p.798-806 |
| issn | 0887-6924 1476-5551 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_4890642 |
| source | Springer Link |
| subjects | 3' Untranslated Regions Acute lymphoblastic leukemia Acute lymphocytic leukemia Animals Basic Helix-Loop-Helix Transcription Factors - genetics Basic Helix-Loop-Helix Transcription Factors - metabolism Care and treatment Cdc4 protein Cell Cycle Proteins - genetics Cell Cycle Proteins - metabolism Cell Transformation, Neoplastic - genetics Cell Transformation, Neoplastic - metabolism Development and progression F-Box Proteins - genetics F-Box Proteins - metabolism F-Box-WD Repeat-Containing Protein 7 Gene expression Gene Expression Profiling Gene Expression Regulation, Leukemic Genetic aspects Genomic Library Health aspects Hematopoiesis Humans Innovations Leucine Leucine zipper proteins Leukemia Lymphatic leukemia Lymphocytes T Mice MicroRNA MicroRNAs MicroRNAs - genetics MicroRNAs - metabolism miRNA Molecular targeted therapy Oncogenes Precursor T-Cell Lymphoblastic Leukemia-Lymphoma - genetics Precursor T-Cell Lymphoblastic Leukemia-Lymphoma - metabolism Precursor T-Cell Lymphoblastic Leukemia-Lymphoma - pathology Primary Cell Culture Proto-Oncogene Proteins - genetics Proto-Oncogene Proteins - metabolism Proto-Oncogene Proteins c-myb - genetics Proto-Oncogene Proteins c-myb - metabolism Ribonucleic acid RNA Signal Transduction T cell receptors T-Cell Acute Lymphocytic Leukemia Protein 1 T-Lymphocytes - metabolism T-Lymphocytes - pathology Transcriptome Transformations Translocation Tumor suppressor genes Tumors Ubiquitin-Protein Ligases - genetics Ubiquitin-Protein Ligases - metabolism |
| title | MicroRNA-193b-3p acts as a tumor suppressor by targeting the MYB oncogene in T-cell acute lymphoblastic leukemia |
| url | http://sfxeu10.hosted.exlibrisgroup.com/loughborough?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-09-21T04%3A43%3A36IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=MicroRNA-193b-3p%20acts%20as%20a%20tumor%20suppressor%20by%20targeting%20the%20MYB%20oncogene%20in%20T-cell%20acute%20lymphoblastic%20leukemia&rft.jtitle=Leukemia&rft.au=Mets,%20E&rft.date=2015-04-01&rft.volume=29&rft.issue=4&rft.spage=798&rft.epage=806&rft.pages=798-806&rft.issn=0887-6924&rft.eissn=1476-5551&rft_id=info:doi/10.1038/leu.2014.276&rft_dat=%3Cgale_pubme%3EA410904298%3C/gale_pubme%3E%3Cgrp_id%3Ecdi_FETCH-LOGICAL-c602t-c6717f4c95c5852059085f7362b49383b98a52ea73b7faf6d4cb5bedf8e40af33%3C/grp_id%3E%3Coa%3E%3C/oa%3E%3Curl%3E%3C/url%3E&rft_id=info:oai/&rft_pqid=1672072777&rft_id=info:pmid/25231743&rft_galeid=A410904298&rfr_iscdi=true |