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Tumor Biology

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27.01.2016 | Original Article

Downregulation of the WT1 gene expression via TMPyP4 stabilization of promoter G-quadruplexes in leukemia cells

verfasst von: Saeedeh Ghazaey Zidanloo, Abasalt Hosseinzadeh Colagar, Hossein Ayatollahi, Jahan-Bakhsh Raoof

Erschienen in: Tumor Biology | Ausgabe 7/2016

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Abstract

The WT1 gene is an important oncogene, and its overexpression is considered as an effective target for anticancer therapy. Regulation of its gene transcription is one way for WT1-targeting drug design. Recently, in silico analysis of some oncogene promoters like WT1 showed some guanine-rich regions with the ability to form G-quadruplex structures. Ligands like 5,10,15,20-tetra(N-methyl-4-pyridyl)-porphine (TMPyP4) have predominant effect on G-quadruplex stabilization. The aim of this study was to understand the effect of TMPyP4 on WT1 gene transcription via stabilization of promoter G-quadruplexes. We examined the formation of new G-quadruplex motifs in WT1 promoter in the presence of TMPyP4. In order to understand the nature of its interaction with WT1 promoter quadruplexes, differential pulse voltammetry (DPV), circular dichroism (CD), polyacrylamide gel electrophoresis, electrophoretic mobility shift assay (EMSA), polymerase chain reaction (PCR) stop assays, and quantitative RT-PCR were performed. According to the results, the WT1 promoter can form stable intramolecular parallel G-quadruplexes. In addition, after 48 and 96 h of incubation, 100 μM TMPyP4 reduced the WT1 transcription to 9 and 0.4 %, respectively, compare to control. We report that ligand-mediated stabilization of G-quadruplexes within the WT1 promoter can silence WT1 expression. This study might offer the basis for the reasonable design and improvement of new porphyrin derivatives as effective anti-leukemia agents for cancer therapy.

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Titel: Downregulation of the WT1 gene expression via TMPyP4 stabilization of promoter G-quadruplexes in leukemia cells
verfasst von: Saeedeh Ghazaey Zidanloo
Abasalt Hosseinzadeh Colagar
Hossein Ayatollahi
Jahan-Bakhsh Raoof
Publikationsdatum: 27.01.2016
Verlag: Springer Netherlands
Erschienen in: Tumor Biology / Ausgabe 7/2016
Print ISSN: 1010-4283
Elektronische ISSN: 1423-0380
DOI: https://doi.org/10.1007/s13277-016-4881-9

Springer Medizin

Downregulation of the WT1 gene expression via TMPyP4 stabilization of promoter G-quadruplexes in leukemia cells

Abstract

Neu im Fachgebiet Onkologie

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Springer Medizin

Abstract

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