اباصلت حسین زاده کلاگر

اصل مقاله فارسی ندارد: G-quadruplexes are displaying potential as new targets for anticancer therapies. Precisely, G-quadruplexes in the proximal promoter region of oncogenes have the promise to act as silencer elements and by that means turn off transcription; So they have emerged as important new drug targets. Thus, ligands that are capable of binding to and stabilizing G-quadruplexes, promise great advantage. Wilms' tumor (WT1) is overexpressed in the greater number of acute leukemia (AML) patients and has been anticipated as a universal diagnostic marker for detection of impending relapse. In this report, we describe two recent studies from our labs. Foremost, we performed an in silico search to find conserved putative G-quadruplex sequences within proximal promoter regions of the human WT1 gene. In the first case, we use TMPyP4 as a reference G-quadruplex ligand to stabilize the structure of G-quadruplex in the WT1 promoter. TMPyP4 was found to bind preferentially to higher-order G-quadruplex species and stabilized them. In the second case, we use different assays to demonstrate that the effect of two FDA-approved anti-AML drugs Daunorubicin and Mitoxantrone on WT1 gene expression level and repression of the oncogene transcription. To find out the effect of ligands on G-quadruplex structures in the WT1 promoter, we used WT21 synthetic oligonucleotides and study the structure formation by differential pulse voltammetry (DPV), circular dichroism (CD), polyacrylamide gel electrophoresis, electrophoretic mobility shifts assay (EMSA), polymerase chain reaction (PCR) stop assays. For WT1 expression level study, quantitative RT-PCR was performed in K562 cell line. Results showed that we might stabilize G-quadruplex structure within WT1 promote region and down-regulate its over-expression in leukemia cell line. We conclude that ligand-mediated stabilization of G-quadruplexes within the WT1 promoter can silence WT1 expression. Overall, the results suggest that targeting