<i>miR-15</i> and <i>miR-16</i> induce apoptosis by targeting BCL2
Amelia CimminoDepartment of Molecular Virology, Immunology, and Medical Genetics and Comprehensive Cancer Center, Ohio State University, Columbus OH 43210; Department of Experimental and Diagnostic Medicine, Interdepartment Center for Cancer Research, University of Ferrara, Ferrara 44100, Italy; Diagnostics of Lymphoproliferative Diseases, Instiuto Nazionale per la Ricerca sul Cancro, Oncologia Medica C, Genoa 16123, Italy; and Department of Medicine, University of California at San Diego, La Jolla, CA 92093George A. CalinDepartment of Molecular Virology, Immunology, and Medical Genetics and Comprehensive Cancer Center, Ohio State University, Columbus OH 43210; Department of Experimental and Diagnostic Medicine, Interdepartment Center for Cancer Research, University of Ferrara, Ferrara 44100, Italy; Diagnostics of Lymphoproliferative Diseases, Instiuto Nazionale per la Ricerca sul Cancro, Oncologia Medica C, Genoa 16123, Italy; and Department of Medicine, University of California at San Diego, La Jolla, CA 92093Muller FabbriDepartment of Molecular Virology, Immunology, and Medical Genetics and Comprehensive Cancer Center, Ohio State University, Columbus OH 43210; Department of Experimental and Diagnostic Medicine, Interdepartment Center for Cancer Research, University of Ferrara, Ferrara 44100, Italy; Diagnostics of Lymphoproliferative Diseases, Instiuto Nazionale per la Ricerca sul Cancro, Oncologia Medica C, Genoa 16123, Italy; and Department of Medicine, University of California at San Diego, La Jolla, CA 92093Marilena V. IorioDepartment of Molecular Virology, Immunology, and Medical Genetics and Comprehensive Cancer Center, Ohio State University, Columbus OH 43210; Department of Experimental and Diagnostic Medicine, Interdepartment Center for Cancer Research, University of Ferrara, Ferrara 44100, Italy; Diagnostics of Lymphoproliferative Diseases, Instiuto Nazionale per la Ricerca sul Cancro, Oncologia Medica C, Genoa 16123, Italy; and Department of Medicine, University of California at San Diego, La Jolla, CA 92093Manuela FerracinDepartment of Molecular Virology, Immunology, and Medical Genetics and Comprehensive Cancer Center, Ohio State University, Columbus OH 43210; Department of Experimental and Diagnostic Medicine, Interdepartment Center for Cancer Research, University of Ferrara, Ferrara 44100, Italy; Diagnostics of Lymphoproliferative Diseases, Instiuto Nazionale per la Ricerca sul Cancro, Oncologia Medica C, Genoa 16123, Italy; and Department of Medicine, University of California at San Diego, La Jolla, CA 92093Masayoshi ShimizuDepartment of Molecular Virology, Immunology, and Medical Genetics and Comprehensive Cancer Center, Ohio State University, Columbus OH 43210; Department of Experimental and Diagnostic Medicine, Interdepartment Center for Cancer Research, University of Ferrara, Ferrara 44100, Italy; Diagnostics of Lymphoproliferative Diseases, Instiuto Nazionale per la Ricerca sul Cancro, Oncologia Medica C, Genoa 16123, Italy; and Department of Medicine, University of California at San Diego, La Jolla, CA 92093Sylwia E. WojcikDepartment of Molecular Virology, Immunology, and Medical Genetics and Comprehensive Cancer Center, Ohio State University, Columbus OH 43210; Department of Experimental and Diagnostic Medicine, Interdepartment Center for Cancer Research, University of Ferrara, Ferrara 44100, Italy; Diagnostics of Lymphoproliferative Diseases, Instiuto Nazionale per la Ricerca sul Cancro, Oncologia Medica C, Genoa 16123, Italy; and Department of Medicine, University of California at San Diego, La Jolla, CA 92093Rami I. AqeilanDepartment of Molecular Virology, Immunology, and Medical Genetics and Comprehensive Cancer Center, Ohio State University, Columbus OH 43210; Department of Experimental and Diagnostic Medicine, Interdepartment Center for Cancer Research, University of Ferrara, Ferrara 44100, Italy; Diagnostics of Lymphoproliferative Diseases, Instiuto Nazionale per la Ricerca sul Cancro, Oncologia Medica C, Genoa 16123, Italy; and Department of Medicine, University of California at San Diego, La Jolla, CA 92093Simona ZupoDepartment of Molecular Virology, Immunology, and Medical Genetics and Comprehensive Cancer Center, Ohio State University, Columbus OH 43210; Department of Experimental and Diagnostic Medicine, Interdepartment Center for Cancer Research, University of Ferrara, Ferrara 44100, Italy; Diagnostics of Lymphoproliferative Diseases, Instiuto Nazionale per la Ricerca sul Cancro, Oncologia Medica C, Genoa 16123, Italy; and Department of Medicine, University of California at San Diego, La Jolla, CA 92093Mariella DonoDepartment of Molecular Virology, Immunology, and Medical Genetics and Comprehensive Cancer Center, Ohio State University, Columbus OH 43210; Department of Experimental and Diagnostic Medicine, Interdepartment Center for Cancer Research, University of Ferrara, Ferrara 44100, Italy; Diagnostics of Lymphoproliferative Diseases, Instiuto Nazionale per la Ricerca sul Cancro, Oncologia Medica C, Genoa 16123, Italy; and Department of Medicine, University of California at San Diego, La Jolla, CA 92093Laura Z. RassentiDepartment of Molecular Virology, Immunology, and Medical Genetics and Comprehensive Cancer Center, Ohio State University, Columbus OH 43210; Department of Experimental and Diagnostic Medicine, Interdepartment Center for Cancer Research, University of Ferrara, Ferrara 44100, Italy; Diagnostics of Lymphoproliferative Diseases, Instiuto Nazionale per la Ricerca sul Cancro, Oncologia Medica C, Genoa 16123, Italy; and Department of Medicine, University of California at San Diego, La Jolla, CA 92093Hansjüerg AlderDepartment of Molecular Virology, Immunology, and Medical Genetics and Comprehensive Cancer Center, Ohio State University, Columbus OH 43210; Department of Experimental and Diagnostic Medicine, Interdepartment Center for Cancer Research, University of Ferrara, Ferrara 44100, Italy; Diagnostics of Lymphoproliferative Diseases, Instiuto Nazionale per la Ricerca sul Cancro, Oncologia Medica C, Genoa 16123, Italy; and Department of Medicine, University of California at San Diego, La Jolla, CA 92093Stefano VoliniaCenter for Cancer ResearchChang‐Gong LiuDepartment of Molecular Virology, Immunology, and Medical Genetics and Comprehensive Cancer Center, Ohio State University, Columbus OH 43210; Department of Experimental and Diagnostic Medicine, Interdepartment Center for Cancer Research, University of Ferrara, Ferrara 44100, Italy; Diagnostics of Lymphoproliferative Diseases, Instiuto Nazionale per la Ricerca sul Cancro, Oncologia Medica C, Genoa 16123, Italy; and Department of Medicine, University of California at San Diego, La Jolla, CA 92093Thomas J. KippsDepartment of Molecular Virology, Immunology, and Medical Genetics and Comprehensive Cancer Center, Ohio State University, Columbus OH 43210; Department of Experimental and Diagnostic Medicine, Interdepartment Center for Cancer Research, University of Ferrara, Ferrara 44100, Italy; Diagnostics of Lymphoproliferative Diseases, Instiuto Nazionale per la Ricerca sul Cancro, Oncologia Medica C, Genoa 16123, Italy; and Department of Medicine, University of California at San Diego, La Jolla, CA 92093Massimo NegriniDepartment of Molecular Virology, Immunology, and Medical Genetics and Comprehensive Cancer Center, Ohio State University, Columbus OH 43210; Department of Experimental and Diagnostic Medicine, Interdepartment Center for Cancer Research, University of Ferrara, Ferrara 44100, Italy; Diagnostics of Lymphoproliferative Diseases, Instiuto Nazionale per la Ricerca sul Cancro, Oncologia Medica C, Genoa 16123, Italy; and Department of Medicine, University of California at San Diego, La Jolla, CA 92093Carlo M. CroceDepartment of Molecular Virology, Immunology, and Medical Genetics and Comprehensive Cancer Center, Ohio State University, Columbus OH 43210; Department of Experimental and Diagnostic Medicine, Interdepartment Center for Cancer Research, University of Ferrara, Ferrara 44100, Italy; Diagnostics of Lymphoproliferative Diseases, Instiuto Nazionale per la Ricerca sul Cancro, Oncologia Medica C, Genoa 16123, Italy; and Department of Medicine, University of California at San Diego, La Jolla, CA 92093
2005en
ABI
Аннотация
Chronic lymphocytic leukemia (CLL) is the most common human leukemia and is characterized by predominantly nondividing malignant B cells overexpressing the antiapoptotic B cell lymphoma 2 (Bcl2) protein. miR-15a and miR-16-1 are deleted or down-regulated in the majority of CLLs. Here, we demonstrate that miR-15a and miR-16-1 expression is inversely correlated to Bcl2 expression in CLL and that both microRNAs negatively regulate Bcl2 at a posttranscriptional level. BCL2 repression by these microRNAs induces apoptopsis in a leukemic cell line model. Therefore, miR-15 and miR-16 are natural antisense Bcl2 interactors that could be used for therapy of Bcl2-overexpressing tumors.
Перевод пока недоступен
Идентификаторы
Цитирования и источники
Цитирований: 2Использованных источников: 0