Stabilization of G-quadruplexes in Intronic Hematopoietic-specific Enhancer of WT1 gene with G-quadruplex targeting ligands: in silico and in vitro techniques
Abstract: 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
- Standort
-
Deutsche Nationalbibliothek Frankfurt am Main
- Umfang
-
Online-Ressource
- Sprache
-
Englisch
- Anmerkungen
-
Indian journal of biochemistry and biophysics. - 61 (2024) , 67-74, ISSN: 0975-0959
- Ereignis
-
Veröffentlichung
- (wo)
-
Freiburg
- (wer)
-
Universität
- (wann)
-
2024
- Urheber
- DOI
-
10.56042/ijbb.v61i2.1377
- URN
-
urn:nbn:de:bsz:25-freidok-2532001
- Rechteinformation
-
Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
- Letzte Aktualisierung
-
25.03.2025, 13:43 MEZ
Datenpartner
Deutsche Nationalbibliothek. Bei Fragen zum Objekt wenden Sie sich bitte an den Datenpartner.
Beteiligte
- Zidanloo, Saeedeh Ghazaey
- Bagherian, Zahra
- Universität
Entstanden
- 2024