Hepigenetics: A Review of Epigenetic Modulators and Potential Therapies in Hepatocellular Carcinoma

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Abstract

Hepatocellular carcinoma is the fifth most common cancer worldwide and the second most lethal, following lung cancer. Currently applied therapeutic practices rely on surgical resection, chemotherapy and radiotherapy, or a combination thereof. These treatment options are associated with extreme adversities, and risk/benefit ratios do not always work in patients' favor. Anomalies of the epigenome lie at the epicenter of aberrant molecular mechanisms by which the disease develops and progresses. Modulation of these anomalous events poses a promising prospect for alternative treatment options, with an abundance of felicitous results reported in recent years. Herein, the most recent epigenetic modulators in hepatocellular carcinoma are recapitulated on.

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Overview of MicroRNA Biogenesis, Mechanisms of Actions, and Circulation

Jacob O'Brien, Heyam Hayder, Yara Zayed … (2018)

MicroRNAs (miRNAs) are a class of non-coding RNAs that play important roles in regulating gene expression. The majority of miRNAs are transcribed from DNA sequences into primary miRNAs and processed into precursor miRNAs, and finally mature miRNAs. In most cases, miRNAs interact with the 3′ untranslated region (3′ UTR) of target mRNAs to induce mRNA degradation and translational repression. However, interaction of miRNAs with other regions, including the 5′ UTR, coding sequence, and gene promoters, have also been reported. Under certain conditions, miRNAs can also activate translation or regulate transcription. The interaction of miRNAs with their target genes is dynamic and dependent on many factors, such as subcellular location of miRNAs, the abundancy of miRNAs and target mRNAs, and the affinity of miRNA-mRNA interactions. miRNAs can be secreted into extracellular fluids and transported to target cells via vesicles, such as exosomes, or by binding to proteins, including Argonautes. Extracellular miRNAs function as chemical messengers to mediate cell-cell communication. In this review, we provide an update on canonical and non-canonical miRNA biogenesis pathways and various mechanisms underlying miRNA-mediated gene regulations. We also summarize the current knowledge of the dynamics of miRNA action and of the secretion, transfer, and uptake of extracellular miRNAs.

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Cancer epigenetics: from mechanism to therapy.

Mark Dawson, Tony Kouzarides (2012)

The epigenetic regulation of DNA-templated processes has been intensely studied over the last 15 years. DNA methylation, histone modification, nucleosome remodeling, and RNA-mediated targeting regulate many biological processes that are fundamental to the genesis of cancer. Here, we present the basic principles behind these epigenetic pathways and highlight the evidence suggesting that their misregulation can culminate in cancer. This information, along with the promising clinical and preclinical results seen with epigenetic drugs against chromatin regulators, signifies that it is time to embrace the central role of epigenetics in cancer. Copyright © 2012 Elsevier Inc. All rights reserved.

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The DNA methyltransferases of mammals.

T Bestor (2000)

The biological significance of 5-methylcytosine was in doubt for many years, but is no longer. Through targeted mutagenesis in mice it has been learnt that every protein shown by biochemical tests to be involved in the establishment, maintenance or interpretation of genomic methylation patterns is encoded by an essential gene. A human genetic disorder (ICF syndrome) has recently been shown to be caused by mutations in the DNA methyltransferase 3B (DNMT3B) gene. A second human disorder (Rett syndrome) has been found to result from mutations in the MECP2 gene, which encodes a protein that binds to methylated DNA. Global genome demethylation caused by targeted mutations in the DNA methyltransferase-1 (Dnmt1) gene has shown that cytosine methylation plays essential roles in X-inactivation, genomic imprinting and genome stabilization. The majority of genomic 5-methylcytosine is now known to enforce the transcriptional silence of the enormous burden of transposons and retroviruses that have accumulated in the mammalian genome. It has also become clear that programmed changes in methylation patterns are less important in the regulation of mammalian development than was previously believed. Although a number of outstanding questions have yet to be answered (one of these questions involves the nature of the cues that designate sites for methylation at particular stages of gametogenesis and early development), studies of DNA methyltransferases are likely to provide further insights into the biological functions of genomic methylation patterns.

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Author and article information

Contributors

Anwar Abdelnaser:

ORCID: https://orcid.org/0000-0003-0088-6799

Journal

Journal ID (nlm-ta): Biomed Res Int

Journal ID (iso-abbrev): Biomed Res Int

Journal ID (publisher-id): BMRI

Title: BioMed Research International

Publisher: Hindawi

ISSN (Print): 2314-6133

ISSN (Electronic): 2314-6141

Publication date Collection: 2020

Publication date (Electronic): 24 November 2020

Volume: 2020

Electronic Location Identifier: 9593254

Affiliations

¹Biotechnology Graduate Program, School of Science and Engineering, The American University in Cairo, Cairo, Egypt

²Institute of Global Health and Human Ecology, School of Science and Engineering, The American University in Cairo, Cairo, Egypt

Author notes

Academic Editor: Junyan Tao

Author information

Mohamed H. Yousef https://orcid.org/0000-0002-9560-4856

Hassan A. N. El-Fawal https://orcid.org/0000-0002-9694-0405

Anwar Abdelnaser https://orcid.org/0000-0003-0088-6799

Article

DOI: 10.1155/2020/9593254

PMC ID: 7707949

PubMed ID: 33299889

SO-VID: 54a385fa-4095-4fdc-954c-6d50e58c8bce

License:

This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

History

Date received : 11 August 2020

Date revision received : 13 October 2020

Date accepted : 5 November 2020

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Hepigenetics: A Review of Epigenetic Modulators and Potential Therapies in Hepatocellular Carcinoma

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Reviews of mathematical modeling in cancer

Most cited references 298

Overview of MicroRNA Biogenesis, Mechanisms of Actions, and Circulation

Cancer epigenetics: from mechanism to therapy.

The DNA methyltransferases of mammals.

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