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

Cancer Gene Therapy volume 28, pages 157–174 (2021)Cite this article

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Abstract

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.

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Fig. 1: Restoration of epi-miRNAs expression might lead to the upregulation of tumor suppressor genes and finally inhibit the malignant capacity of tumor cells, including suppression of cell proliferation, invasion, and migration, and also induction of cell apoptosis and sensitivity to chemotherapy.

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Authors and Affiliations

  1. Department of medical Genetics, School of Medicine, Bam University of Medical Sciences, Bam, Iran

    Mohammad Reza Karimzadeh

  2. Iranian Red Crescent Society, Tehran, Iran

    Peyman Pourdavoud

  3. Department of Genetics and Molecular Biology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran

    Naeim Ehtesham & Meysam Mosallaei

  4. Department of Biology, Faculty of Sciences, Arak University, Arak, Iran

    Mohaddese Qadbeigi

  5. Non-Communicable Diseases Research Center, Endocrinology and Metabolism Research Institute, Tehran University of Medical Sciences, Tehran, Iran

    Masood Movahedi Asl

  6. Department of Applied Cell Sciences, Faculty of Medicine, Kashan University of Medical Sciences, Kashan, Iran

    Behrang Alani

  7. Department of Internal Medicine, School of Medicine, Isfahan University of Medical Science, Isfahan, Iran

    Bahram Pakzad

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  1. Mohammad Reza Karimzadeh
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  2. Peyman Pourdavoud
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  4. Mohaddese Qadbeigi
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  5. Masood Movahedi Asl
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  6. Behrang Alani
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  7. Meysam Mosallaei
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  8. Bahram Pakzad
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Correspondence to Bahram Pakzad.

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Karimzadeh, M.R., Pourdavoud, P., Ehtesham, N. et al. Regulation of DNA methylation machinery by epi-miRNAs in human cancer: emerging new targets in cancer therapy. Cancer Gene Ther 28, 157–174 (2021). https://doi.org/10.1038/s41417-020-00210-7

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  • DOI: https://doi.org/10.1038/s41417-020-00210-7

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