Document Detail


Targeting of the signal transducer Smo links microRNA-326 to the oncogenic Hedgehog pathway in CD34(+) CML stem/progenitor cells.
MedLine Citation:
PMID:  23341351     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Aberrant expression and function of microRNAs (miRNAs) in leukemia have added a new layer of complexity to the understanding of development and progression of the disease state. However, their targeting of specific signaling pathways responsible for the maintenance and survival properties of leukemic stem cell (LSC) still remains to be further clarified. Hedgehog (Hh) signaling, a highly conserved developmental pathway, has been proven as a functional pathway for LSCs, and loss of this pathway impairs the development of BCR-ABL-induced chronic myeloid leukemia (CML) and depletes CML stem cells. Here we revealed that up-regulation of the Hh signal transducer Smo was associated with reduced expression of miR-326 in the CD34(+) cells from a group of patients with CML at diagnosis. Additionally, overexpression of miR-326 led to down-regulation of Smo, resulted in decreased cell proliferation and elevated rate of apoptosis in CML CD34(+) cells. Interestingly, restoration of Smo expression levels reversed the effect of miR-326 and rescued K562 cells from the anti-proliferative effects of this miRNA. Thus, Smo appears to be an essential target of miR-326 during the pathogenesis of CML. These findings lead us to suggest that down-regulation of miR-326 may be a possible mechanism for unrestricted activation of Smo signal transducer of the oncogenic Hh pathway in CML; therefore, the restoration of miR-326 expression could be of benefit in eradicating CD34(+) CML stem/progenitor cells that represent a potential source of relapse in patients suffering CML. © 2013 Wiley Periodicals, Inc.
Authors:
Sadegh Babashah; Majid Sadeghizadeh; Abbas Hajifathali; Mostafa Rezaei Tavirani; Mina Soufi Zomorod; Mojtaba Ghadiani; Masoud Soleimani
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2013-1-23
Journal Detail:
Title:  International journal of cancer. Journal international du cancer     Volume:  -     ISSN:  1097-0215     ISO Abbreviation:  Int. J. Cancer     Publication Date:  2013 Jan 
Date Detail:
Created Date:  2013-1-23     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0042124     Medline TA:  Int J Cancer     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2013 UICC.
Affiliation:
Department of Molecular Genetics, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, Iran.
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