Multiple G-quadruplex binding ligand induced transcriptomic map of cancer cell lines

Area of Science:

• Genomics and Molecular Biology
• DNA Structure and Function
• Cancer Research

Background:

• G-quadruplexes (G4s) are non-canonical DNA structures involved in critical genomic processes like replication and gene expression regulation.
• Altered G4 formation is implicated in genomic instability and diseases, including cancers and neurodegenerative disorders.
• G4s are enriched in cis-regulatory elements of oncogenes, driving the search for G4-DNA binding ligands (G4DBLs) to modulate gene expression.

Purpose of the Study:

• To analyze the G4DBL-responsive transcriptome in various cancer cell lines to assess the specificity of novel G4DBLs.
• To identify a core set of genes consistently regulated by multiple G4DBLs across different cancer types.
• To establish a foundational dataset for future comparative analyses of G4DBLs based on cis-regulatory G4-associated gene expression.

Main Methods:

• Assembly of differentially regulated transcripts in response to various G4DBLs.
• Identification of a core gene set regulated by three or more G4DBLs across diverse cancer cell lines.
• Utilizing existing knowledge of G4DBL mechanisms (topology shifts, folding, disruption).

Main Results:

• A dataset of transcripts differentially regulated by distinct G4DBLs was compiled.
• A core set of genes was identified that are commonly regulated by multiple G4DBLs in diverse cancer cell lines.
• This work provides a basis for understanding G4DBL-specific gene regulation in cancer.

Conclusions:

• Analysis of G4DBL-responsive transcriptomes is essential for evaluating G4DBL specificity in cancer.
• The identified core gene set offers insights into common regulatory pathways targeted by G4DBLs.
• This dataset serves as a platform for future comparative studies of G4DBLs in cancer therapeutics.