Down-regulation of hsa-miR-10a in chronic myeloid leukemia CD34+ cells increases USF2-mediated cell growth.
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.
Agirre
Xabier
X
Foundation for Applied Medical Research, Division of Cancer, Clínica Universitaria, University of Navarre, Pamplona, Spain.
Jiménez-Velasco
Antonio
A
San José-Enériz
Edurne
E
Garate
Leire
L
Bandrés
Eva
E
Cordeu
Lucia
L
Aparicio
Oscar
O
Saez
Borja
B
Navarro
Germán
G
Vilas-Zornoza
Amaia
A
Pérez-Roger
Ignacio
I
García-Foncillas
Jesús
J
Torres
Antonio
A
Heiniger
Anabel
A
Calasanz
María José
MJ
Fortes
Puri
P
Román-Gómez
José
J
Prósper
Felipe
F
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*
D018952:Antigens, CD34; D035683:MicroRNAs; D051720:Upstream Stimulatory Factors; C533097:MIR150, human; C497184:USF2 protein, human