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

Universidad de Navarra, Iruña, Navarre, Spain
Molecular Cancer Research (Impact Factor: 4.5). 01/2009; 6(12):1830-40. DOI: 10.1158/1541-7786.MCR-08-0167
Source: PubMed

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.

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    • "This miRNA down regulates ABL1, including infusion with BCR. [33] miR-224/326/422b/520a Down regulated in IM-responding CML patients [44] miR-564 BCR/ABL-dependent down regulation in CML cells [39] a c t a h a e m a t o l o g i c a p o l o n i c a x x x ( 2 0 1 3 ) x x x – x x x "
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    ABSTRACT: Chronic myeloid leukemia (CML) is a malignant disease of progenitor myeloid cells caused by chromosomal translocation that results in the forming of diminutive Philadephia chromosome that harbors BCR/ABL fusion oncogene. The product of this oncogene, a tyrosine kinase, alters several important regulatory pathways related to cell growth and differentiation thus leading to cancer transformation. Major form of CML therapy is based on tyrosine kinase inhibitors, first of all imatinib (IM). Some patients develop resistance to IM in the course of treatment. In the process of leukemogenesis the activity of miRNAs – one of groups of RNAs involved in RNA interference (RNAi) – is altered. Signatures of altered miRNAs activity may serve as a prognostic factor in the development and therapy of several diseases. Moreover, other group of RNAs involved in RNAi – siRNA – might be valuable addition to array of specific therapeutics targeted the BCR/ABL kinase.
    Acta haematologica Polonica 10/2013; DOI:10.1016/j.achaem.2013.07.001
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    • "Based on reports that miR-150 downregulation is associated with chronic myeloid leukemia (Agirre et al., 2008; Machová Poláková et al., 2011), we have tried to transfect mir-150 by PEG–PEI-based nanoparticles into leukemia cells. Different types of PEI with varying molecular weights were used for gene delivery. "
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    ABSTRACT: MicroRNAs (miRNAs) are acknowledged as indispensable regulators relevant in many biological processes, and they have been pioneered as therapeutic targets for curing disease. miRNAs are single-stranded, small (19-22 nt) regulatory non-coding RNAs whose deregulation of expression triggers human cancers,including leukemias, mainly through dysregulation of expression of leukemia genes. miRNAs can function as tumor suppressors (suppressing malignant potential) or oncogenes (activating malignant potential) like actors of complex diseases. To address the issue of overcoming instability and low transfection efficiency in vitro, the polyethylene glycol-polyethyleneimine (PEG-PEI) nanoparticle was used as non-viral vector carrier for miR-150 transfection, which is downregulated in chronic myeloid leukemia. PEG-PEI [PEG(550)3 -g-PEI(1800) ]/miRNA nanocomplexes were synthesized and characterized by particle size distribution, polydispersity index and zeta potential, surface charge, their cytotoxicity, and transfection efficiency. Interaction with human leukemia cells (K-562 and KU812) and control cells NCI-BL2347 with them has been investigated. The transfection efficiency of PEG-PEI/miRNA at N/P 26 rose 6.7 fold above the control by qRT-PCR. The size of homogenous nanocomplexes (PBI < 0.5) was 160.8 ± 11 nm. The data indicate that PEG-PEI may be an encouraging non-viral carrier for altering miRNA expression in the treatment of chronic myeloid leukemia, with many advantages such as relatively high miRNA transfection efficiency and low cytotoxicity.
    Cell Biology International 08/2013; 37(11). DOI:10.1002/cbin.10157 · 1.64 Impact Factor
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    • "miR-10a Human Cell proliferation Agirre, et al. 2008 33 NF1 miR-10b Human metastasis Chai, et al. 2010 49 HDAC4 miR-10a Human Differentiation Huang, et al. 2010 16 KLF4 miR-10b Human Cell motility Tian, et al. 2010 51 TIAM1 miR-10b Human invasion and migration moriarty, et al. 2010 47 SFRS1 miR-10a/b Human Splicing meseguer, et al. 2010 22 MAP37K miR-10a Human inflammation Fang, et al. 2010 19 β-TRC miR-10a Human inflammation Fang, et al. 2010 19 NCOR2 miR-10a/b Human Neurite outgrowth Foley, et al. 2011 23 Transcriptional enhancement Ribosomal protein mRNAs miR-10a mouse Global protein synthesis Ørom, et al. 2008 52 Transcriptional regulation HOXD4 miR-10a Human Tan, et al. 2009 RNA "
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    ABSTRACT: The miR-10 microRNA precursor family encodes a group of short non-coding RNAs involved in gene regulation. The miR-10 family is highly conserved and has sparked the interest of many research groups because of the genomic localization in the vicinity of, coexpression with and regulation of the Hox gene developmental regulators. Here, we review the current knowledge of the evolution, physiological function and involvement in cancer of this family of microRNAs.
    RNA biology 09/2011; 8(5):728-34. DOI:10.4161/rna.8.5.16324 · 5.38 Impact Factor
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