title: Src homology 2 domain-containing inositol-5-phosphatase and CCAAT enhancer-binding protein beta are targeted by miR-155 in B cells of Emicro-MiR-155 transgenic mice.
abstract: We showed that Emicro-MiR-155 transgenic mice develop acute lymphoblastic leukemia/high-grade lymphoma. Most of these leukemias start at approximately 9 months irrespective of the mouse strain. They are preceded by a polyclonal pre-B-cell proliferation, have variable clinical presentation, are transplantable, and develop oligo/monoclonal expansion. In this study, we show that in these transgenic mice the B-cell precursors have the highest MiR-155 transgene expression and are at the origin of the leukemias. We determine that Src homology 2 domain-containing inositol-5-phosphatase (SHIP) and CCAAT enhancer-binding protein beta (C/EBPbeta), 2 important regulators of the interleukin-6 signaling pathway, are direct targets of MiR-155 and become gradually more down-regulated in the leukemic than in the preleukemic mice. We hypothesize that miR-155, by down-modulating Ship and C/EBPbeta, initiates a chain of events that leads to the accumulation of large pre-B cells and acute lymphoblastic leukemia/high-grade lymphoma.
authors.affiliation: Comprehensive Cancer Center, The Ohio State University, Columbus, OH 43210, USA.
authors.forename: Stefan
authors.initials: S
authors.lastname: Costinean
authors.forename: Sukhinder K
authors.initials: SK
authors.lastname: Sandhu
authors.forename: Irene M
authors.initials: IM
authors.lastname: Pedersen
authors.forename: Esmerina
authors.initials: E
authors.lastname: Tili
authors.forename: Rossana
authors.initials: R
authors.lastname: Trotta
authors.forename: Danilo
authors.initials: D
authors.lastname: Perrotti
authors.forename: David
authors.initials: D
authors.lastname: Ciarlariello
authors.forename: Paolo
authors.initials: P
authors.lastname: Neviani
authors.forename: Jason
authors.initials: J
authors.lastname: Harb
authors.forename: Lauren Rachel
authors.initials: LR
authors.lastname: Kauffman
authors.forename: Aaditya
authors.initials: A
authors.lastname: Shidham
authors.forename: Carlo Maria
authors.initials: CM
authors.lastname: Croce
mesh_terms: D000818:Animals; D022782:CCAAT-Enhancer-Binding Protein-beta / Q000096:biosynthesis* / Q000235:genetics; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism*; D015536:Down-Regulation / Q000235:genetics; D015973:Gene Expression Regulation, Leukemic / Q000235:genetics; D000072181:Inositol Polyphosphate 5-Phosphatases; D015850:Interleukin-6 / Q000378:metabolism; D016393:Lymphoma, B-Cell / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D035683:MicroRNAs / Q000096:biosynthesis* / Q000235:genetics; D010744:Phosphoric Monoester Hydrolases / Q000096:biosynthesis* / Q000235:genetics; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics / Q000378:metabolism*; D054448:Precursor Cells, B-Lymphoid / Q000378:metabolism*; D015398:Signal Transduction / Q000235:genetics
chemical_list: D022782:CCAAT-Enhancer-Binding Protein-beta; D015850:Interleukin-6; D035683:MicroRNAs; C532623:Mirn155 microRNA, mouse; D010744:Phosphoric Monoester Hydrolases; D000072181:Inositol Polyphosphate 5-Phosphatases