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.

Overexpression of microRNA-16-2 contributes to the abnormalerythropoiesis in polycythemia vera / Guglielmelli, P.; Tozzi, L.; Bogani, C.; Iacobucci, I.; Ponziani, V.; Martinelli, G.; Bosi, A.; Vannucchi, A.M. .. - In: BLOOD. - ISSN 0006-4971. - STAMPA. - 117(25):(2011), pp. 6923-6927. [10.1182/blood-2010-09-306506]

Overexpression of microRNA-16-2 contributes to the abnormalerythropoiesis in polycythemia vera.

GUGLIELMELLI, PAOLA;TOZZI, LORENZO;BOGANI, COSTANZA;PONZIANI, VANESSA;BOSI, ALBERTO;VANNUCCHI, ALESSANDRO MARIA
2011

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.
2011
117(25)
6923
6927
Guglielmelli, P.; Tozzi, L.; Bogani, C.; Iacobucci, I.; Ponziani, V.; Martinelli, G.; Bosi, A.; Vannucchi, A.M. .
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Utilizza questo identificatore per citare o creare un link a questa risorsa: https://hdl.handle.net/2158/596420
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