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

• 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
• ISSN: 0929-1903; 1476-5500
• DOI: 10.1038/s41417-020-00210-7

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.