Regulation of DNA methylation machinery by epi-miRNAs in human cancer: emerging new targets in cancer therapy

Disruption in DNA methylation processes can lead to alteration in gene expression and function that would ultimately result in malignant transformation. In this way, studies have shown that, in cancers, methylation-associated silencing inactivates tumor suppressor genes, as effectively as mutations....

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Bibliographic Details
Published in:Cancer gene therapy 2021-04, Vol.28 (3-4), p.157-174
Main Authors: Karimzadeh, Mohammad Reza, Pourdavoud, Peyman, Ehtesham, Naeim, Qadbeigi, Mohaddese, Asl, Masood Movahedi, Alani, Behrang, Mosallaei, Meysam, Pakzad, Bahram
Format: Article
Language:English
Subjects:
13/2
13/89
631/67/68
692/699/67
Biomedical and Life Sciences
Biomedicine
Cancer
Cancer cells
Cancer therapies
Carcinogenesis
Care and treatment
Cytosine
Deoxyribonucleic acid
DNA
DNA Methylation
Gene Expression
Gene Therapy
Genetic aspects
Genetic regulation
Health aspects
Humans
Methylation
Methyltransferases
MicroRNA
MicroRNAs - genetics
miRNA
Neoplasms - genetics
Neoplasms - therapy
Oncology, Experimental
Review Article
Tumor suppressor genes
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Summary:Disruption in DNA methylation processes can lead to alteration in gene expression and function that would ultimately result in malignant transformation. In this way, studies have shown that, in cancers, methylation-associated silencing inactivates tumor suppressor genes, as effectively as mutations. DNA methylation machinery is composed of several genes, including those with DNA methyltransferases activity, proteins that bind to methylated cytosine in the promoter region, and enzymes with demethylase activity. Based on a prominent body of evidence, DNA methylation machinery could be regulated by microRNAs (miRNAs) called epi-miRNAs. Numerous studies demonstrated that dysregulation in DNA methylation regulators like upstream epi-miRNAs is indispensable for carcinogenesis; consequently, the malignant capacity of these cells could be reversed by restoring of this regulatory system in cancer. Conceivably, recognition of these epi-miRNAs in cancer cells could not only reveal novel molecular entities in carcinogenesis, but also render promising targets for cancer therapy. In this review, at first, we have an overview of the methylation alteration in cancers, and the effect of this phenomenon in miRNAs expression and after that, we conduct an in-depth discussion about the regulation of DNA methylation regulators by epi-miRNAs in cancer cells.
ISSN:0929-1903
1476-5500
DOI:10.1038/s41417-020-00210-7