title: miR-15 and miR-16 induce apoptosis by targeting BCL2.
abstract: 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.
authors.affiliation: Department of Molecular Virology, Immunology, and Medical Genetics and Comprehensive Cancer Center, Ohio State University, Columbus OH 43210, USA.
authors.forename: Amelia
authors.initials: A
authors.lastname: Cimmino
authors.forename: George Adrian
authors.initials: GA
authors.lastname: Calin
authors.forename: Muller
authors.initials: M
authors.lastname: Fabbri
authors.forename: Marilena V
authors.initials: MV
authors.lastname: Iorio
authors.forename: Manuela
authors.initials: M
authors.lastname: Ferracin
authors.forename: Masayoshi
authors.initials: M
authors.lastname: Shimizu
authors.forename: Sylwia E
authors.initials: SE
authors.lastname: Wojcik
authors.forename: Rami I
authors.initials: RI
authors.lastname: Aqeilan
authors.forename: Simona
authors.initials: S
authors.lastname: Zupo
authors.forename: Mariella
authors.initials: M
authors.lastname: Dono
authors.forename: Laura
authors.initials: L
authors.lastname: Rassenti
authors.forename: Hansjuerg
authors.initials: H
authors.lastname: Alder
authors.forename: Stefano
authors.initials: S
authors.lastname: Volinia
authors.forename: Chang-Gong
authors.initials: CG
authors.lastname: Liu
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Kipps
authors.forename: Massimo
authors.initials: M
authors.lastname: Negrini
authors.forename: Carlo M
authors.initials: CM
authors.lastname: Croce
mesh_terms: D017209:Apoptosis / Q000235:genetics; D049109:Cell Proliferation; D015973:Gene Expression Regulation, Leukemic; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000235:genetics* / Q000378:metabolism; D035683:MicroRNAs / Q000235:genetics / Q000502:physiology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics* / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: C505361:MIRN15 microRNA, human; C505362:MIRN16 microRNA, human; D035683:MicroRNAs; D019253:Proto-Oncogene Proteins c-bcl-2