title: Overexpression of microRNA-16-2 contributes to the abnormal erythropoiesis in polycythemia vera.
abstract: Deregulated expression of microRNAs is associated with neoplasia. Here, we show that mature miR-16 levels are abnormally increased in CD34(+) cells of patients with polycythemia vera as a consequence of preferential expression of miR-16-2 on chromosome 3 rather than of miR-16-1 on chromosome 13. Forced expression of miRNA-16 in normal CD34(+) cells stimulated erythroid cell proliferation and maturation. Conversely, exposure of polycythemia vera CD34(+) cells to small interfering RNA against pre-miR-16-2 reduced erythroid colonies and largely prevented formation of erythropoietin-independent colonies; myeloid progenitors remained unaffected. Experiments with knock down of JAK2 indicated that overexpression of miR-16 was independent of JAK/STAT pathway activation. Mice injected with an miR-16 antagomir showed a blunted erythroid response to exogenous erythropoietin, which indicates a role of miR-16 in normal erythropoiesis. These data suggest that deregulation of miR-16-2 contributes to abnormal expansion of erythroid lineage in polycythemia vera. However, the mechanisms for miR-16-2 overexpression remain to be elucidated, because no genetic abnormalities at the miR-16-2 locus were discovered.
authors.affiliation: Department of Hematology, University of Florence, Florence, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Guglielmelli
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Tozzi
authors.forename: Costanza
authors.initials: C
authors.lastname: Bogani
authors.forename: Ilaria
authors.initials: I
authors.lastname: Iacobucci
authors.forename: Vanessa
authors.initials: V
authors.lastname: Ponziani
authors.forename: Giovanni
authors.initials: G
authors.lastname: Martinelli
authors.forename: Alberto
authors.initials: A
authors.lastname: Bosi
authors.forename: Alessandro M
authors.initials: AM
authors.lastname: Vannucchi
mesh_terms: D000818:Animals; D018952:Antigens, CD34 / Q000276:immunology; D041905:Erythroid Cells / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D004920:Erythropoiesis; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000235:genetics*; D011087:Polycythemia Vera / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology*; D015854:Up-Regulation
chemical_list: D018952:Antigens, CD34; C505362:MIRN16 microRNA, human; D035683:MicroRNAs; C522604:Mirn16 microRNA, mouse