title: miR-203 and miR-221 regulate SOCS1 and SOCS3 in essential thrombocythemia.
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.
authors.affiliation: Molecular Oncology and Embryology Laboratory, Human Anatomy Unit, School of Medicine, University of Barcelona, IDIBAPS, Barcelona, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Navarro
authors.affiliation: Department of Pathology, Hospital del Mar, IDIBAPS, Barcelona, Spain.|Grup de Recerca Clínica Aplicada en Neoplàsies Hematològiques, IMIM (Hospital del Mar Medical Research Institute), IDIBAPS, Barcelona, Spain.
authors.forename: S
authors.initials: S
authors.lastname: Pairet
authors.affiliation: Grup de Recerca Clínica Aplicada en Neoplàsies Hematològiques, IMIM (Hospital del Mar Medical Research Institute), IDIBAPS, Barcelona, Spain.|Department of Hematology, Hospital del Mar, IDIBAPS, Barcelona, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Álvarez-Larrán
authors.affiliation: Grup de Recerca Clínica Aplicada en Neoplàsies Hematològiques, IMIM (Hospital del Mar Medical Research Institute), IDIBAPS, Barcelona, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Pons
authors.affiliation: Institute of Hematology and Oncology, Hospital Clinic, IDIBAPS, Barcelona, Spain.
authors.forename: G
authors.initials: G
authors.lastname: Ferrer
authors.affiliation: Department of Pathology, Hospital del Mar, IDIBAPS, Barcelona, Spain.|Grup de Recerca Clínica Aplicada en Neoplàsies Hematològiques, IMIM (Hospital del Mar Medical Research Institute), IDIBAPS, Barcelona, Spain.
authors.forename: R
authors.initials: R
authors.lastname: Longarón
authors.affiliation: Grup de Recerca Clínica Aplicada en Neoplàsies Hematològiques, IMIM (Hospital del Mar Medical Research Institute), IDIBAPS, Barcelona, Spain.
authors.forename: C
authors.initials: C
authors.lastname: Fernández-Rodríguez
authors.affiliation: Grup de Recerca Clínica Aplicada en Neoplàsies Hematològiques, IMIM (Hospital del Mar Medical Research Institute), IDIBAPS, Barcelona, Spain.
authors.forename: L
authors.initials: L
authors.lastname: Camacho
authors.affiliation: Molecular Oncology and Embryology Laboratory, Human Anatomy Unit, School of Medicine, University of Barcelona, IDIBAPS, Barcelona, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Monzó
authors.affiliation: Grup de Recerca Clínica Aplicada en Neoplàsies Hematològiques, IMIM (Hospital del Mar Medical Research Institute), IDIBAPS, Barcelona, Spain.|Department of Hematology, Hospital del Mar, IDIBAPS, Barcelona, Spain.
authors.forename: C
authors.initials: C
authors.lastname: Besses
authors.affiliation: Department of Pathology, Hospital del Mar, IDIBAPS, Barcelona, Spain.|Department of Hematology, Hospital del Mar, IDIBAPS, Barcelona, Spain.
authors.forename: B
authors.initials: B
authors.lastname: Bellosillo
mesh_terms: D016000:Cluster Analysis; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D006801:Humans; D053614:Janus Kinase 2 / Q000235:genetics; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D034622:RNA Interference; D015203:Reproducibility of Results; D050791:STAT Transcription Factors / Q000378:metabolism; D015398:Signal Transduction; D000071222:Suppressor of Cytokine Signaling 1 Protein; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000235:genetics*; D013920:Thrombocythemia, Essential / Q000235:genetics* / Q000378:metabolism
chemical_list: D053614:Janus Kinase 2; D035683:MicroRNAs; D050791:STAT Transcription Factors; D000071222:Suppressor of Cytokine Signaling 1 Protein; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins; C546703:MIRN203 microRNA, human; C525709:MIR221, human; C108944:SOCS1 protein, human; C106644:SOCS3 protein, human