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

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Journal of Cell Communication and Signaling Aims and scope

Abstract

The G-quadruplexes (G4s) are a class of DNA secondary structures with guanine rich DNA sequences that can fold into four stranded non-canonical structures. At the genomic level, their pivotal role is well established in DNA replication, telomerase functions, constitution of topologically associating domains, and the regulation of gene expression. Genome instability mediated by altered G4 formation and assembly has been associated with multiple disorders including cancers and neurodegenerative disorders. Multiple tools have also been developed to predict the potential G4 regions in genomes and the whole genome G4 maps are also being derived through sequencing approaches. Enrichment of G4s in the cis-regulatory elements of genes associated with tumorigenesis has accelerated the quest for identification of G4-DNA binding ligands (G4DBLs) that can selectively bind and regulate the expression of such specific genes. In this context, the analysis of G4DBL responsive transcriptome in diverse cancer cell lines is inevitable for assessment of the specificity of novel G4DBLs. Towards this, we assembled the transcripts differentially regulated by different G4DBLs and have also identified a core set of genes regulated in diverse cancer cell lines in response to 3 or more of these ligands. With the mode of action of G4DBLs towards topology shifts, folding, or disruption of G4 structure being currently visualized, we believe that this dataset will serve as a platform for assembly of G4DBL responsive transcriptome for comparative analysis of G4DBLs in multiple cancer cells based on the expression of specific cis-regulatory G4 associated genes in the future.

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Fig. 1
Fig. 2

Data availability

The 25,228 temporal differential gene regulation events in response to 7 G4DBLs (with their diverse concentrations and stimulation time points) in six different human cancer cell lines is provided in the ‘.xlsx’ format (Supplementary table 1).

Abbreviations

G4:

G-quadruplex

G4DBLs:

G4-DNA binding ligands

TMPyP4:

5,10,15,20–Tetrakis(N-methyl-4-pyridyl)porphyrin

TMPyP4-PT:

Metallated analogues of TMPyP4 with Zn(II), Pt(II)

360A:

2-N,6-N-Bis(1-methylquinolin-1-ium-3-yl)pyridine-2,6-dicarboxamide

AQ1:

4-[(7-Chloroquinolin-4-yl)amino]-2-(diethylaminomethyl)phenol

CMO3:

Phenanthroline-1,3,6,8 (2H,7H)-tetraone

PhenDC3:

N2,N9-Bis(1-Methylquinolin-3-Yl)-1,10-Phenanthroline-2,9-Dicarboxamide

APTO-253:

L2-(5-fluoro-2-methyl-1H-indol-3-yl)-1H-imidazo[4,5f][1,10]phenanthroline;hydrochloride

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Acknowledgements

Amjesh Revikumar is a recipient of National Post-Doctoral Fellowship (PDF/2017/001652) from the Science and Engineering Research Board, Department of Science and Technology (DST), Government of India. Rajesh Raju is a recipient of the Young Scientist Award (YSS/2014/000607) from the Science and Engineering Research Board, Department of Science and Technology (DST), Government of India. Anjana Aravind is a recipient of the Junior Research Fellowship from the Council of Scientific & Industrial Research (CSIR), Government of India. Akhina Palollathil is a recipient of Junior Research Fellowship from the University Grants Commission (UGC), Government of India.

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Authors and Affiliations

  1. Cancer Research Program, Rajiv Gandhi Centre for Biotechnology, Thiruvananthapuram, 695014, India

    Amjesh Revikumar, Rajeswari Raguraman & Rajesh Raju

  2. Center for Systems Biology and Molecular Medicine, Yenepoya Research Centre, Yenepoya (Deemed To Be University), Mangalore, 575018, India

    Vivek Kashyap, Akhina Palollathil, Anjana Aravind, Thottethodi Subrahmanya Keshava Prasad & Rajesh Raju

  3. Health Science Centre, University of Oklahoma, Oklahoma City, USA

    Rajeswari Raguraman

  4. Department of Surgical Oncology, Yenepoya Medical College, Yenepoya (Deemed to Be University), Mangalore, 575018, India

    Kenkere Mallikarjunaiah Kiran Kumar & Manavalan Vijayakumar

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  1. Amjesh Revikumar
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Revikumar, A., Kashyap, V., Palollathil, A. et al. Multiple G-quadruplex binding ligand induced transcriptomic map of cancer cell lines. J. Cell Commun. Signal. 16, 129–135 (2022). https://doi.org/10.1007/s12079-021-00637-z

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