Down-Regulation of hsa-miR-10a in Chronic Myeloid Leukemia CD34+ Cells Increases USF2-Mediated Cell Growth

摘要

MicroRNAs (miRNA) are small noncoding,single-stranded RNAs that inhibit gene expression at aposttranscriptional level, whose abnormal expressionhas been described in different tumors. The aim of ourstudy was to identify miRNAs potentially implicatedin chronic myeloid leukemia (CML). We detected anabnormal miRNA expression profile in mononuclear andCD34+ cells from patients with CML compared withhealthy 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 dependenton BCR-ABL1 activity and contributed to the increasedcell growth of CML cells. We identified the upstreamstimulatory factor 2 (USF2) as a potential target ofhsa-miR-10a and showed that overexpression of USF2also increases cell growth. The clinical relevance ofthese findings was shown in a group of 85 newlydiagnosed patients with CML in which expression ofhsa-miR-10a was down-regulated in 71% of the patients,whereas expression of USF2 was up-regulated in 60% ofthe CML patients, with overexpression of USF2 beingsignificantly associated with decreased expression ofhsa-miR-10a (P = 0.004). Our results indicate thatdown-regulation of hsa-miR-10a may increase USF2 andcontribute to the increase in cell proliferation of CMLimplicating a miRNA in the abnormal behavior of CML.