Targeting proto-oncogene B-MYB G-quadruplex with a nucleic acid–based fluorescent probe

The B-MYB gene encodes a transcription factor (B-MYB) that regulates cell growth and survival. Abnormal expression of B-MYB is frequently observed in lung cancer and poses challenges for targeted drug therapy. Oncogenes often contain DNA structures called G-quadruplexes (G4s) in their promoter regio...

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Bibliographic Details
Published in:International journal of biological macromolecules 2024-05, Vol.266 (Pt 1), p.131055-131055, Article 131055
Main Authors: Lourenço, Pedro, Miranda, André, Campello, Maria Paula Cabral, Paulo, António, Louis-Mergny, Jean, Cruz, Carla
Format: Article
Language:English
Subjects:
Acridines - chemistry
Acridines - pharmacology
B-MYB
Cell Cycle Proteins
Fluorescent Dyes - chemistry
G-quadruplex, Acridine-MYB probe
G-Quadruplexes
Humans
Ligands
Promoter Regions, Genetic
Proto-Oncogene Mas
Trans-Activators - chemistry
Trans-Activators - genetics
Trans-Activators - metabolism
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Summary:The B-MYB gene encodes a transcription factor (B-MYB) that regulates cell growth and survival. Abnormal expression of B-MYB is frequently observed in lung cancer and poses challenges for targeted drug therapy. Oncogenes often contain DNA structures called G-quadruplexes (G4s) in their promoter regions, and B-MYB is no exception. These G4s play roles in genetic regulation and are potential cancer treatment targets. In this study, a probe was designed to specifically identify a G4 within the promoter region of the B-MYB gene. This probe combines an acridine derivative ligand with a DNA segment complementary to the target sequence, enabling it to hybridize with the adjacent sequence of the G4 being investigated. Biophysical studies demonstrated that the acridine derivative ligands C5NH2 and C8NH2 not only effectively stabilized the G4 structure but also exhibited moderate affinity. They were capable of altering the G4 topology and exhibited enhanced fluorescence emission in the presence of this quadruplex. Additionally, these ligands increased the number of G4s observed in cellular studies. Through various biophysical studies, the target sequence was shown to form a G4 structure, even with an extra nucleotide tail added to its flanking region. Cellular studies confirmed the co-localization between the target sequence and the developed probe.
ISSN:0141-8130
1879-0003
DOI:10.1016/j.ijbiomac.2024.131055