miR-203 and miR-221 regulate SOCS1 and SOCS3 in essential thrombocythemia.

Navarro, A.; Pairet García, Silvia; Álvarez Larrán, Alberto; Pons, A.; Ferrer, G.; Longarón Rozalen, Raquel; Fernández Rodríguez, M. Concepción; Camacho Díaz, Laura; Monzó, M.; Besses Raebel, Carles; Bellosillo Paricio, Beatriz

miR-203 and miR-221 regulate SOCS1 and SOCS3 in essential thrombocythemia.

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dc.contributor.author Navarro, A.ca
dc.contributor.author Pairet García, Silviaca
dc.contributor.author Álvarez Larrán, Albertoca
dc.contributor.author Pons, A.ca
dc.contributor.author Ferrer, G.ca
dc.contributor.author Longarón Rozalen, Raquelca
dc.contributor.author Fernández Rodríguez, M. Concepciónca
dc.contributor.author Camacho Díaz, Lauraca
dc.contributor.author Monzó, M.ca
dc.contributor.author Besses Raebel, Carlesca
dc.contributor.author Bellosillo Paricio, Beatrizca
dc.date.accessioned 2016-04-14T11:10:34Z
dc.date.available 2016-09-30T02:00:05Z
dc.date.issued 2016
dc.description.abstract The biological basis of essential thrombocythemia (ET) patients lacking known mutations is still unknown. MicroRNAs (miRNA) regulate hematopoietic differentiation and are deregulated in several hematopoietic malignancies. However, miRNA expression in ET patients has been poorly explored. We performed miRNA profiling in platelets from 19 ET patients and 10 healthy controls. Hierarchical cluster analysis showed two well-separated clusters between patients and controls, indicating that ET platelets had a characteristic 70-miRNA signature (P<0.0001), 68 of which were downregulated. According to the mutational status, three differentially expressed miRNAs, miR-15a (P=0.045), miR-150 (P=0.001) and miR-519a (P=0.036), were identified. A 40-miRNA signature was identified characterizing JAK2V617F-positive ET patients. Eight genes, whose interaction with the miRNAs could activate the JAK/STAT pathway were identified. An inverse correlation was observed between miRNAs expression and their target genes for SOCS1 and miR-221, SOCS3 and miR-221, SOCS3 and miR-203, and PTPN11 and miR-23a. All three miRNAs were upregulated in JAK2V617F-negative ET patients. SOCS1 and SOCS3 were validated as targets of miR-221 and miR-203, respectively. In summary, our study shows that platelets from JAK2V617F-negative ET patients harbor a specific miRNA signature that can participate in the modulation of the JAK/STAT pathway through regulation of key genes as SOCS1 and SOCS3.ca
dc.description.sponsorship This work was supported by grants from Instituto de Salud Carlos III FEDER(PI10/01807, PI13/00557, PI13/00393, RD12/0036/0010, PT13/0010/0005), 2014 SGR567, and the‘Xarxa de Bancs de tumors’sponsored by Pla Director d'Oncologia deCatalunya (XBTC). Concepción Fernández-Rodríguez received a fellowship from theMinistry of Economy and Competitiveness of Spain (PFIS grant FI11/00353).
dc.format.mimetype application/pdfca
dc.identifier.citation Navarro A, Pairet S, Álvarez-Larrán A, Pons A, Ferrer G, Longarón R et al. miR-203 and miR-221 regulate SOCS1 and SOCS3 in essential thrombocythemia. Blood Cancer J. 2016 Mar 18;6:e406. DOI: 10.1038/bcj.2016.10.ca
dc.identifier.doi http://dx.doi.org/10.1038/bcj.2016.10
dc.identifier.issn 2044-5385
dc.identifier.uri http://hdl.handle.net/10230/26087
dc.language.iso engca
dc.publisher Nature Publishing Groupca
dc.relation.ispartof Blood Cancer Journal. 2016 Mar 18;6:e406
dc.rights.accessRights info:eu-repo/semantics/openAccess
dc.subject.other Trombocitèmiaca
dc.title miR-203 and miR-221 regulate SOCS1 and SOCS3 in essential thrombocythemia.ca
dc.type info:eu-repo/semantics/articleca
dc.type.version info:eu-repo/semantics/publishedVersionca

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