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Stabilization of G-quadruplexes in Intronic Hematopoietic-specific Enhancer of WT1 gene with G-quadruplex targeting ligands: in silico and in vitro techniques

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Title Stabilization of G-quadruplexes in Intronic Hematopoietic-specific Enhancer of WT1 gene with G-quadruplex targeting ligands: in silico and in vitro techniques
 
Creator Zidanloo, Saeedeh Ghazaey
Bagherian, Zahra
 
Subject Daunorubic n
G-quadruplex
Mitoxantrone
TMPyP4
WT1 intronic hematopoietic-specific enhancer
 
Description 67-74
Wilms’ tumor 1 (WT1) gene was identified as a tumor-suppressor gene in childhood renal neoplasm, Wilms' tumor, and has an important impact on cell growth and differentiation. So, mutations in WT1 and its over-expression related to not only Wilms’ tumor but also other tumors and leukemias. WT1’s intronic hematopoietic-specific enhancer is GC-rich

and could form G-quadruplex structures. Herein,

we study the

effect of three G-quadruplex

stabilizing ligands

on the formation and stability of G-quadruplex structures in WT1 intronic hematopoietic-specific enhancer. We designed

a truncated sequence

of WT1 intronic enhancer (named WT1-I33) with

the highest likelihood score of

G-quadruplex formation and study the effect of different concentrations of TMPyP4, daunorubicin, and mitoxantrone on

G-quadruplex formation in WT1-I33

oligonucleotide

using in silico and cell-free

assays. The

results revealed

that

WT1-I33 has the potential to form G-quadruplex structures and these structures in WT1 hematopoietic-specific enhancer could be stabilized by the ligands. According to the role of enhancers in transcription, stabilizing of G-quadruplex structures could make the enhancer inaccessible for the transcription factors and transcription of the WT1 gene might be

downregulated. These

data could help emerge novel gene-specific

therapeutic strategies and selective targeting of

G-quadruplex structures.
 
Date 2024-02-06T07:44:48Z
2024-02-06T07:44:48Z
2024-02
 
Type Article
 
Identifier 0975-0959 (Online); 0301-1208 (Print)
http://nopr.niscpr.res.in/handle/123456789/63311
https://doi.org/:10.56042/ijbb.v61i2.1377
 
Language en
 
Publisher NIScPR-CSIR, India
 
Source IJBB Vol.61(02) [February 2024]