MicroRNA-650 expression is influenced by immunoglobulin gene rearrangement and affects the biology of chronic lymphocytic leukemia
MicroRNAs (miRNAs) play a key role in chronic lymphocytic leukemia as well as in normal B cells. Notably, miRNA gene encoding miR-650 and its homologs overlap with several variable (V) subgenes coding for lambda immunoglobulin (IgLλ). Recent studies describe the role of miR-650 in solid tumors, but...
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| Veröffentlicht in: | Blood 2012-03, Vol.119 (9), p.2110-2113 |
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| creator | Mraz, Marek Dolezalova, Dasa Plevova, Karla Stano Kozubik, Katerina Mayerova, Veronika Cerna, Katerina Musilova, Katerina Tichy, Boris Pavlova, Sarka Borsky, Marek Verner, Jan Doubek, Michael Brychtova, Yvona Trbusek, Martin Hampl, Ales Mayer, Jiri Pospisilova, Sarka |
| description | MicroRNAs (miRNAs) play a key role in chronic lymphocytic leukemia as well as in normal B cells. Notably, miRNA gene encoding miR-650 and its homologs overlap with several variable (V) subgenes coding for lambda immunoglobulin (IgLλ). Recent studies describe the role of miR-650 in solid tumors, but its role in chronic lymphocytic leukemia (CLL) has not yet been studied. Our experiments demonstrate that miR-650 expression is regulated by coupled expression with its host gene for IgLλ. This coupling provides a unique yet unobserved mechanism for microRNA gene regulation. We determine that higher expression of miR-650 is associated with a favorable CLL prognosis and influences the proliferation capacity of B cells. We also establish that in B cells, miR-650 targets proteins important in cell proliferation and survival: cyclin dependent kinase 1 (CDK1), inhibitor of growth 4 (ING4), and early B-cell factor 3 (EBF3). This study underscores the importance of miR-650 in CLL biology and normal B-cell physiology. |
| doi_str_mv | 10.1182/blood-2011-11-394874 |
| format | Article |
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Notably, miRNA gene encoding miR-650 and its homologs overlap with several variable (V) subgenes coding for lambda immunoglobulin (IgLλ). Recent studies describe the role of miR-650 in solid tumors, but its role in chronic lymphocytic leukemia (CLL) has not yet been studied. Our experiments demonstrate that miR-650 expression is regulated by coupled expression with its host gene for IgLλ. This coupling provides a unique yet unobserved mechanism for microRNA gene regulation. We determine that higher expression of miR-650 is associated with a favorable CLL prognosis and influences the proliferation capacity of B cells. We also establish that in B cells, miR-650 targets proteins important in cell proliferation and survival: cyclin dependent kinase 1 (CDK1), inhibitor of growth 4 (ING4), and early B-cell factor 3 (EBF3). This study underscores the importance of miR-650 in CLL biology and normal B-cell physiology.</description><identifier>ISSN: 0006-4971</identifier><identifier>EISSN: 1528-0020</identifier><identifier>DOI: 10.1182/blood-2011-11-394874</identifier><identifier>PMID: 22234685</identifier><language>eng</language><publisher>Washington, DC: Elsevier Inc</publisher><subject>Adult ; Aged ; Aged, 80 and over ; Biological and medical sciences ; Cell Cycle - genetics ; Cell Line, Tumor ; Female ; Gene Expression Regulation ; Gene Rearrangement ; Genes, Immunoglobulin ; Genes, Immunoglobulin Light Chain ; Hematologic and hematopoietic diseases ; Humans ; Leukemia, Lymphocytic, Chronic, B-Cell - genetics ; Leukemia, Lymphocytic, Chronic, B-Cell - mortality ; Leukemias. Malignant lymphomas. Malignant reticulosis. 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This study underscores the importance of miR-650 in CLL biology and normal B-cell physiology.</description><subject>Adult</subject><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Biological and medical sciences</subject><subject>Cell Cycle - genetics</subject><subject>Cell Line, Tumor</subject><subject>Female</subject><subject>Gene Expression Regulation</subject><subject>Gene Rearrangement</subject><subject>Genes, Immunoglobulin</subject><subject>Genes, Immunoglobulin Light Chain</subject><subject>Hematologic and hematopoietic diseases</subject><subject>Humans</subject><subject>Leukemia, Lymphocytic, Chronic, B-Cell - genetics</subject><subject>Leukemia, Lymphocytic, Chronic, B-Cell - mortality</subject><subject>Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis</subject><subject>Male</subject><subject>Medical sciences</subject><subject>MicroRNAs - genetics</subject><subject>Middle Aged</subject><subject>Neoplasm Staging</subject><subject>Prognosis</subject><issn>0006-4971</issn><issn>1528-0020</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2012</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kU2LFDEQhoMo7rj6D0RyEU-t-exOX4Rl8QtWBdFzSNKVmWg6GZNuca7-cjM7o96EQKrgqbzFE4QeU_KcUsVe2Jjz1DFCadcOH4UaxB20oZKpjhBG7qINIaTvxDjQC_Sg1q-EUMGZvI8uGGNc9Epu0K_3wZX86cNV10uC4ee-QK0hJxwqDsnHFZKDCdsDDvO8pryN2a4xJLyFBLiAKcWkLcyQFmzShI334JaKlx1gG3LM2wPOHrtdySk4HA_zfpfdYTnWsH6DOZiH6J43scKj832Jvrx-9fn6bXfz8c2766ubzgk-LN3k5KBk77gH70bJrQLOFZ8MWEcEeEqEGrkdJsX7UYzeckZEqwxTA5N24pfo2endfcnfV6iLnkN1EKNJkNeqR9ZTKQemGilOZFNTawGv9yXMphw0JfooX9_K10f5rdcn-W3syTlgtTNMf4f-2G7A0zNgqjPRN3Uu1H_cMZ1T0riXJw6ajh8Biq4u3H5EKM2unnL4_ya_AQ1SpOQ</recordid><startdate>20120301</startdate><enddate>20120301</enddate><creator>Mraz, Marek</creator><creator>Dolezalova, Dasa</creator><creator>Plevova, Karla</creator><creator>Stano Kozubik, Katerina</creator><creator>Mayerova, Veronika</creator><creator>Cerna, Katerina</creator><creator>Musilova, Katerina</creator><creator>Tichy, Boris</creator><creator>Pavlova, Sarka</creator><creator>Borsky, Marek</creator><creator>Verner, Jan</creator><creator>Doubek, Michael</creator><creator>Brychtova, Yvona</creator><creator>Trbusek, Martin</creator><creator>Hampl, Ales</creator><creator>Mayer, Jiri</creator><creator>Pospisilova, Sarka</creator><general>Elsevier Inc</general><general>Americain Society of Hematology</general><scope>6I.</scope><scope>AAFTH</scope><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>20120301</creationdate><title>MicroRNA-650 expression is influenced by immunoglobulin gene rearrangement and affects the biology of chronic lymphocytic leukemia</title><author>Mraz, Marek ; Dolezalova, Dasa ; Plevova, Karla ; Stano Kozubik, Katerina ; Mayerova, Veronika ; Cerna, Katerina ; Musilova, Katerina ; Tichy, Boris ; Pavlova, Sarka ; Borsky, Marek ; Verner, Jan ; Doubek, Michael ; Brychtova, Yvona ; Trbusek, Martin ; Hampl, Ales ; Mayer, Jiri ; Pospisilova, Sarka</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c437t-dc57856c3fefc953b8e3383daebc04ef104893b7d836949fb3204694a28725bd3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2012</creationdate><topic>Adult</topic><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>Biological and medical sciences</topic><topic>Cell Cycle - genetics</topic><topic>Cell Line, Tumor</topic><topic>Female</topic><topic>Gene Expression Regulation</topic><topic>Gene Rearrangement</topic><topic>Genes, Immunoglobulin</topic><topic>Genes, Immunoglobulin Light Chain</topic><topic>Hematologic and hematopoietic diseases</topic><topic>Humans</topic><topic>Leukemia, Lymphocytic, Chronic, B-Cell - genetics</topic><topic>Leukemia, Lymphocytic, Chronic, B-Cell - mortality</topic><topic>Leukemias. 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| subjects | Adult Aged Aged, 80 and over Biological and medical sciences Cell Cycle - genetics Cell Line, Tumor Female Gene Expression Regulation Gene Rearrangement Genes, Immunoglobulin Genes, Immunoglobulin Light Chain Hematologic and hematopoietic diseases Humans Leukemia, Lymphocytic, Chronic, B-Cell - genetics Leukemia, Lymphocytic, Chronic, B-Cell - mortality Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis Male Medical sciences MicroRNAs - genetics Middle Aged Neoplasm Staging Prognosis |
| title | MicroRNA-650 expression is influenced by immunoglobulin gene rearrangement and affects the biology of chronic lymphocytic leukemia |
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