The Role of DNA and RNA Methylation in Cancer: Mechanisms and Therapeutic Potential of Epigenetic and Epitranscriptomic Drugs”

Abstract

Chemical modifications of DNA and RNA play a pivotal role in the regulation of gene expression, enabling precise control of cellular functions and adaptation to changing environmental conditions. The most common modification in human DNA is cytosine methylation at the 5th position (5mC), while in RNA it is adenosine methylation at the N6 position (m⁶A), recognized as the predominant epitranscriptomic modification. Regulation of these modifications relies on the coordinated action of three groups of proteins: methyltransferases, demethylases, and reader proteins, which recognize modified nucleobases and recruit effector protein complexes, thereby translating the pattern of nucleic acid modifications into a specific biological response. Dysfunction of these protein groups leads to aberrant 5mC and m⁶A patterns, which play a crucial role in the pathogenesis and progression of many human diseases, including cancer. Deregulation of DNA and RNA methylation affects, among others, the control of genes involved in proliferation, apoptosis, and genome stability, which may promote tumor progression; moreover, the dynamic and reversible nature of these modifications makes them attractive diagnostic and therapeutic targets in cancer treatment.