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Review
. 2022 Jul 25:9:965924.
doi: 10.3389/fmolb.2022.965924. eCollection 2022.

The potential interplay between G-quadruplex and p53: their roles in regulation of ferroptosis in cancer

Lulu Zhang  1   2 , Yi Lu  1 , Xiaoli Ma  1   2 , Yuanxin Xing  1   2 , Jinbo Sun  3 , Yanfei Jia  1   2
Affiliations
Review

The potential interplay between G-quadruplex and p53: their roles in regulation of ferroptosis in cancer

Lulu Zhang et al. Front Mol Biosci. .

Abstract

Ferroptosis is a novel form of regulated cell death trigged by various biological processes, and p53 is involved in different ferroptosis regulations and functions as a crucial regulator. Both DNA and RNA can fold into G-quadruplex in GC-rich regions and increasing shreds of evidence demonstrate that G-quadruplexes have been associated with some important cellular events. Investigation of G-quadruplexes is thus vital to revealing their biological functions. Specific G-quadruplexes are investigated to discover new effective anticancer drugs. Multiple modulations have been discovered between the secondary structure G-quadruplex and p53, probably further influencing the ferroptosis in cancer. G-quadruplex binds to ferric iron-related structures directly and may affect the p53 pathways as well as ferroptosis in cancer. In addition, G-quadruplex also interacts with p53 indirectly, including iron-sulfur cluster metabolism, telomere homeostasis, lipid peroxidation, and glycolysis. In this review, we summarized the latent interplay between G-quadruplex and p53 which focused mainly on ferroptosis in cancer to provide the potential understanding and encourage future studies.

Keywords: G-quadruplex; biological activities; cancer; ferroptosis; p53.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
Regulation of ferroptosis by p53. Various proteins involved in iron metabolism and lipid peroxidation are modulated by p53.
FIGURE 2
FIGURE 2
Schematic diagram of the regulation network of G-quadruplex and p53 in ferroptosis (Created with BioRender.com).
See this image and copyright information in PMC

References

    1. Adámik M., Kejnovská I., Bažantová P., Petr M., Renčiuk D., Vorlíčková M., et al. (2016). p53 binds human telomeric G-quadruplex in vitro . Biochimie 128-129, 83–91. 10.1016/j.biochi.2016.07.004 - DOI - PubMed
    1. Alam M. M., Lal S., FitzGerald K. E., Zhang L. (2016). A holistic view of cancer bioenergetics: Mitochondrial function and respiration play fundamental roles in the development and progression of diverse tumors. Clin. Transl. Med. 5 (1), 3. 10.1186/s40169-016-0082-9 - DOI - PMC - PubMed
    1. Alvarez S. W., Sviderskiy V. O., Terzi E. M., Papagiannakopoulos T., Moreira A. L., Adams S., et al. (2017). NFS1 undergoes positive selection in lung tumours and protects cells from ferroptosis. Nature 551 (7682), 639–643. 10.1038/nature24637 - DOI - PMC - PubMed
    1. Amparo C., Clark J., Bedell V., Murata-Collins J. L., Martella M., Pichiorri F., et al. (2020). Duplex DNA from sites of helicase-polymerase Uncoupling Links non-B DNA structure formation to replicative stress. Cancer Genomics Proteomics 17 (2), 101–115. 10.21873/cgp.20171 - DOI - PMC - PubMed
    1. Andorf C. M., Kopylov M., Dobbs D., Koch K. E., Stroupe M. E., Lawrence C. J., et al. (2014). G-quadruplex (G4) motifs in the maize (Zea mays L.) genome are enriched at specific Locations in Thousands of genes Coupled to energy status, hypoxia, low sugar, and Nutrient Deprivation. J. Genet. Genomics 41 (12), 627–647. 10.1016/j.jgg.2014.10.004 - DOI - PubMed