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Review
. 2022 Aug 24:13:885635.
doi: 10.3389/fgene.2022.885635. eCollection 2022.

Molecular basis of epigenetic regulation in cancer diagnosis and treatment

Sonam Tulsyan  1 , Mehreen Aftab  1 , Sandeep Sisodiya  1   2 , Asiya Khan  3 , Atul Chikara  1   2 , Pranay Tanwar  3 , Showket Hussain  1
Affiliations
Review

Molecular basis of epigenetic regulation in cancer diagnosis and treatment

Sonam Tulsyan et al. Front Genet. .

Abstract

The global cancer cases and mortality rates are increasing and demand efficient biomarkers for accurate screening, detection, diagnosis, and prognosis. Recent studies have demonstrated that variations in epigenetic mechanisms like aberrant promoter methylation, altered histone modification and mutations in ATP-dependent chromatin remodelling complexes play an important role in the development of carcinogenic events. However, the influence of other epigenetic alterations in various cancers was confirmed with evolving research and the emergence of high throughput technologies. Therefore, alterations in epigenetic marks may have clinical utility as potential biomarkers for early cancer detection and diagnosis. In this review, an outline of the key epigenetic mechanism(s), and their deregulation in cancer etiology have been discussed to decipher the future prospects in cancer therapeutics including precision medicine. Also, this review attempts to highlight the gaps in epigenetic drug development with emphasis on integrative analysis of epigenetic biomarkers to establish minimally non-invasive biomarkers with clinical applications.

Keywords: DNA methylation; cancer; cancer therapies; chromatin remodelling; epigenetics; histone modification.

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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 no conflict of interest.

Figures

FIGURE 1
FIGURE 1
Representative image of epigenetic mechanisms (Template was created by free Biorender.com). (A) Histone modification- Histone methyltransferases (HMT) add methyl groups to histones (H4K20Me3). Histone demethylases (HDM)/Lysine demethylase (KDM6/4) remove these methyl groups. It is associated with both gene expression and silencing. Histone acetylation; The addition of an acetyl group on H3K9Ac (lysine 9 histone H3) in enhancer/promoter region by histone acetylase (HAT) enzyme. Histone deacetylase (HDAC) interact with transcriptional repressor (TR) to remove the modifications. (B) DNA methylation- DNA methyltransferases (DNMTs) add methyl group in the promoter region of genes. On the contrary, DNA hypomethylation indicates overall decrease in the methylation levels as compared to normal cells, and affects the intergenic and intronic regions of the DNA, resulting in chromosomal instability and increased mutation events (C) RNA methylation- Indirect translational repression by miRNA causes deadenylation, in which the 3′ poly(A) tail of an mRNA is removed, leading to increased mRNA degradation. The miRNA–mRNA interaction can lead to several modes of direct translational repression.
FIGURE 2
FIGURE 2
Mechanism of action of epidrugs in anticancer therapies [Icons were created by Biorender.com (accessed on February 9th 2022)].
FIGURE 3
FIGURE 3
Epigenetic biomarkers and different sample types for diagnosis, prognosis, and treatment therapies in different cancers [Icons were created by Biorender.com (accessed on January 28th 2022)].
FIGURE 4
FIGURE 4
Epidrugs in preclinical and clinical trials for cancer therapy [Icons were created by Biorender.com]. (DNMTi - DNA methyl Transferase; HDACi—Histone deacetylase inhibitor; - HMTi -Histone methyltransferase inhibitors; HDMi- Histone demethylase inhibitors and HATi -Histone acetyltransferase inhibitors).
FIGURE 5
FIGURE 5
Diagrammatic representation of research pipeline on the discovery of novel potential epi-markers in human cancers (Template was created by free Biorender.com).
See this image and copyright information in PMC

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