{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T12:22:23Z","timestamp":1790166143166,"version":"4.1.0"},"reference-count":50,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2013,3,13]],"date-time":"2013-03-13T00:00:00Z","timestamp":1363132800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Intl Journal of Cancer"],"published-print":{"date-parts":[[2013,8]]},"abstract":"<jats:p>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\u2010ABL\u2010induced chronic myeloid leukemia (CML) and depletes CML stem cells. Here, we revealed that upregulation of the Hh smoothened (Smo) signal transducer was associated with reduced expression of miR\u2010326 in the CD34<jats:sup>+<\/jats:sup> cells from a group of patients with CML at diagnosis. Additionally, overexpression of miR\u2010326 led to downregulation of Smo, resulted in decreased cell proliferation and elevated rate of apoptosis in CML CD34<jats:sup>+<\/jats:sup> cells. Interestingly, restoration of Smo expression levels reversed the effect of miR\u2010326 and rescued K562 cells from the antiproliferative effects of this miRNA. Thus, Smo appears to be an essential target of miR\u2010326 during the pathogenesis of CML. These findings lead us to suggest that downregulation of miR\u2010326 may be a possible mechanism for unrestricted activation of Smo signal transducer of the oncogenic Hh pathway in CML; therefore, the restoration of miR\u2010326 expression could be of benefit in eradicating CD34<jats:sup>+<\/jats:sup> CML stem\/progenitor cells that represent a potential source of relapse in patients suffering CML.<\/jats:p>","DOI":"10.1002\/ijc.28043","type":"journal-article","created":{"date-parts":[[2013,1,23]],"date-time":"2013-01-23T10:18:07Z","timestamp":1358936287000},"page":"579-589","source":"Crossref","is-referenced-by-count":68,"title":["Targeting of the signal transducer Smo links microRNA\u2010326 to the oncogenic Hedgehog pathway in CD34<sup>+<\/sup> CML stem\/progenitor cells"],"prefix":"10.1002","volume":"133","author":[{"given":"Sadegh","family":"Babashah","sequence":"first","affiliation":[{"name":"Department of Molecular Genetics Faculty of Biological Sciences Tarbiat Modares 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