Biological Relevance and Therapeutic Potential of G-Quadruplexes in Cancer

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Molecular Cancer Biology".

Deadline for manuscript submissions: closed (15 December 2022) | Viewed by 2108

Special Issue Editors

CICS-UBI—Centro de Investigação em Ciências da Saúde, Universidade da Beira Interior, Av. Infante D. Henrique, 6200-506 Covilhã, Portugal
Interests: DNA and RNA G-quadruplexes; G-quadruplexes aptamers; G-quadruplex ligands; biomolecular interactions; biophysical techniques; drug design and development; cancer; drug delivery systems
Special Issues, Collections and Topics in MDPI journals

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Guest Editor
CICS-UBI—Health Science Research Centre, University of Beira Interior, 6200-506 Covilha, Portugal
Interests: biopharmaceuticals; recombinant production; downstream processing; chromatography; gene therapy; gene silencing; health biotechnology
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

DNA and RNA can adopt four-stranded G-quadruplex (G4) structures through self-association of four guanine bases by Hoogsteen hydrogen bonding within a planar G-tetrad.

Self-stacking of two or more G-tetrads generates a G4 structure that is further stabilized by cations (mainly potassium or sodium) and small molecules, which have been evaluated as a novel anti-cancer strategy.

Several biophysical and structural studies evidence G4 formation in regulatory regions, such as human telomeres, oncogene-promoter regions, replication initiation sites, and 5′- and 3′-untranslated regions (UTR) of mRNA. For example, several experiments using molecular and cell biology methods have demonstrated that G4s exist in chromatin DNA and in RNA, linking G4s to biological processes ranging from transcription and translation to genome instability and cancer, emerging as a new class of molecular targets for drug development.

This Special Issue will highlight the DNA and RNA G4s’ biological roles and mechanisms of action to better understand the molecular basis of related diseases as well as to envision the development of novel therapeutic strategies. This will cover both basic and (pre)clinical aspects that will advance our understanding of the possibility to target these structures in human tumors and unravel the relation between G4 formation and lethality of cancer cells to consider G4s as therapeutic targets in cancer.

Dr. Carla Cruz
Dr. Fani Pereira de Sousa
Guest Editors

Manuscript Submission Information

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Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cancers is an international peer-reviewed open access semimonthly journal published by MDPI.

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Keywords

  • DNA and RNA G-quadruplexes
  • G-quadruplex (G4)
  • novel anti-cancer strategy
  • molecular targets
  • cancer

Published Papers (1 paper)

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Research

19 pages, 3321 KiB  
Article
Functional Downregulation of PD-L1 and PD-L2 by CpG and non-CpG Oligonucleotides in Melanoma Cells
by Johannes Kleemann, Katja Steinhorst, Veronika König, Nadja Zöller, Jindrich Cinatl, Jr., Deniz Özistanbullu, Roland Kaufmann, Markus Meissner and Stefan Kippenberger
Cancers 2022, 14(19), 4698; https://doi.org/10.3390/cancers14194698 - 27 Sep 2022
Viewed by 1457
Abstract
The clinical application of immune checkpoint inhibitors represents a breakthrough progress in the treatment of metastasized melanoma and other tumor entities. In the present study, it was hypothesized that oligonucleotides (ODNs), known as modulators of the immune response, have an impact on the [...] Read more.
The clinical application of immune checkpoint inhibitors represents a breakthrough progress in the treatment of metastasized melanoma and other tumor entities. In the present study, it was hypothesized that oligonucleotides (ODNs), known as modulators of the immune response, have an impact on the endogenous expression of checkpoint molecules, namely PD-L1 and PD-L2 (PD-L1/2). IFNγ-stimulated melanoma cells (A375, SK-Mel-28) were treated with different synthetically manufactured oligonucleotides which differed in sequence, length and backbone composition. It was found that a variety of different ODN sequences significantly suppressed PD-L1/2 expression. This effect was dependent on length and phosphorothioate (PTO) backbone. In particular, a sequence containing solely guanines (nCpG-6-PTO) was highly effective in downregulating PD-L1/2 at the protein, mRNA and promoter levels. Mechanistically, we gave evidence that ODNs with G-quartet-forming motifs suppress the interferon signaling axis (JAK/STAT/IRF1). Our findings identify a subset of ODNs as interesting pharmacological compounds that could expand the arsenal of targeted therapies to combat the immunological escape of tumor cells. Full article
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