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Abstract
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Wilms tumor 1 (WT1) has long been overexpressed in acute myeloid leukemia and has a prognostic value in its diagnosis. Lately, the formation of G-quadruplexes in oncogenic promoters like WT1 has been widely investigated since stabilization of these structures leads to transcriptional inhibition of the oncogene. Daunorubicin and mitoxantrone considered as crucial components of almost all standard acute myeloid leukemia induction regimens. Herein we have proposed a probable molecular mechanism of action through which the drugs may stabilize WT1 promoter G-quadruplexes. Differential pulse voltammetry, circular dichroism, and polyacrylamide gel electrophoresis, electrophoretic mobility shifts assay, polymerase chain reaction (PCR) stop assays, and quantitative RT-PCR were performed in order to better understanding the nature of interactions between the drugs and G-quadruplexes. Data revealed that both drugs had potential to stabilize G-quadruplexes and down-regulate WT1 transcription but daunorubicin exposed more silencing impact. The results illustrated the therapeutic association of these two commercial FDA-approved drugs in WT1 transcriptional down-regulation. Since WT1 has known as a transcriptional regulator of at least 137 target genes, so the new data are significant for the development of new approaches to regulating WT1 and other target genes by employing special drugs in cancer treatment.
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