Micro RNAs represent a class of small regulatory non-coding RNAs which are aberrantly expressed in some human malignancies. We here describe specific regulation of miRNA expression in chronic myeloid leukemia (CML) depending on BCR-ABL, the characteristic onco-protein of CML. Using microarray analysis (miCHIP) and miRNA-specific quantitative real-time RT-PCR from CML cell lines treated with either imatinib or anti BCR-ABL shRNAs to inhibit its tyro-sine kinase activity or its protein expression, we found specific down-regulation of miRNAs encoded within the polycistronic miR-17-92 cluster (two- to fivefold). In addition, analysis of miR-17-92 expression in purified normal, early chronic phase and blast crisis CML CD34 + cells demonstrated increased expression in chronic phase but not in blast crisis CML. Lentivirus-mediated over-expression of miR-17-92 encoded miRNAs in K562 cells increases proliferation and enhances sensitivity to imatinib induced cell death. Furthermore, reporter assays using luciferase genes with specific miRNA binding sites in the 3′ untranslated region were used to specifically inhibit miRNA function by so called antagomirs. Finally, strategies to induce stable gain- and loss of function phenotypes for specific miRNAs based on lentiviral transfer of miRNA- and antagomir expression cassettes allow functional analysis for individual miRNAs. Such studies are required to determine whether altered miRNA expression may contribute to the pathophysiology of CML and if so how miRNAs may provide potential targets for therapeutic intervention.
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Scherr, M., Venturini, L., Eder, M. (2008). Expression and Function of microRNAs in Chronic Myeloid Leukemia. In: Ying, SY. (eds) Current Perspectives in microRNAs (miRNA). Springer, Dordrecht. https://doi.org/10.1007/978-1-4020-8533-8_17
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DOI: https://doi.org/10.1007/978-1-4020-8533-8_17
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