title: Down-regulation of hsa-miR-10a in chronic myeloid leukemia CD34+ cells increases USF2-mediated cell growth.
abstract: MicroRNAs (miRNA) are small noncoding, single-stranded RNAs that inhibit gene expression at a posttranscriptional level, whose abnormal expression has been described in different tumors. The aim of our study was to identify miRNAs potentially implicated in chronic myeloid leukemia (CML). We detected an abnormal miRNA expression profile in mononuclear and CD34(+) cells from patients with CML compared with healthy controls. Of 157 miRNAs tested, hsa-miR-10a, hsa-miR-150, and hsa-miR-151 were down-regulated, whereas hsa-miR-96 was up-regulated in CML cells. Down-regulation of hsa-miR-10a was not dependent on BCR-ABL1 activity and contributed to the increased cell growth of CML cells. We identified the upstream stimulatory factor 2 (USF2) as a potential target of hsa-miR-10a and showed that overexpression of USF2 also increases cell growth. The clinical relevance of these findings was shown in a group of 85 newly diagnosed patients with CML in which expression of hsa-miR-10a was down-regulated in 71% of the patients, whereas expression of USF2 was up-regulated in 60% of the CML patients, with overexpression of USF2 being significantly associated with decreased expression of hsa-miR-10a (P = 0.004). Our results indicate that down-regulation of hsa-miR-10a may increase USF2 and contribute to the increase in cell proliferation of CML implicating a miRNA in the abnormal behavior of CML.
authors.affiliation: Foundation for Applied Medical Research, Division of Cancer, Clínica Universitaria, University of Navarre, Pamplona, Spain.
authors.forename: Xabier
authors.initials: X
authors.lastname: Agirre
authors.forename: Antonio
authors.initials: A
authors.lastname: Jiménez-Velasco
authors.forename: Edurne
authors.initials: E
authors.lastname: San José-Enériz
authors.forename: Leire
authors.initials: L
authors.lastname: Garate
authors.forename: Eva
authors.initials: E
authors.lastname: Bandrés
authors.forename: Lucia
authors.initials: L
authors.lastname: Cordeu
authors.forename: Oscar
authors.initials: O
authors.lastname: Aparicio
authors.forename: Borja
authors.initials: B
authors.lastname: Saez
authors.forename: Germán
authors.initials: G
authors.lastname: Navarro
authors.forename: Amaia
authors.initials: A
authors.lastname: Vilas-Zornoza
authors.forename: Ignacio
authors.initials: I
authors.lastname: Pérez-Roger
authors.forename: Jesús
authors.initials: J
authors.lastname: García-Foncillas
authors.forename: Antonio
authors.initials: A
authors.lastname: Torres
authors.forename: Anabel
authors.initials: A
authors.lastname: Heiniger
authors.forename: María José
authors.initials: MJ
authors.lastname: Calasanz
authors.forename: Puri
authors.initials: P
authors.lastname: Fortes
authors.forename: José
authors.initials: J
authors.lastname: Román-Gómez
authors.forename: Felipe
authors.initials: F
authors.lastname: Prósper
mesh_terms: D018952:Antigens, CD34 / Q000378:metabolism; D002455:Cell Division / Q000502:physiology; D045744:Cell Line, Tumor; D015536:Down-Regulation / Q000502:physiology; D020869:Gene Expression Profiling; D015973:Gene Expression Regulation, Leukemic / Q000235:genetics*; D016313:Genes, abl / Q000235:genetics; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology*; D035683:MicroRNAs / Q000737:chemistry / Q000502:physiology*; D009690:Nucleic Acid Conformation; D014162:Transfection; D015854:Up-Regulation / Q000502:physiology; D051720:Upstream Stimulatory Factors / Q000235:genetics*
chemical_list: D018952:Antigens, CD34; D035683:MicroRNAs; D051720:Upstream Stimulatory Factors; C533097:MIR150, human; C497184:USF2 protein, human