For DNA methylation, DNMTs act as writers, TET as an eraser, and Zinc finger proteins as a reader. Similarly, for RNA methylation, METTL3/14, WTAP act as writer, FTO, and ALKBH5 as an eraser, and YTHDF proteins act as a reader. Differential promoter DNA methylation is associated with cancer progression and can have biomarker ability. For example, hypermethylation of tumor suppresser genes such as TFPI2, SOX17, and GATA4 and hypomethylation of oncogenes such as SPP1, AIM2, and PTHLH can act as biomarker for oral cancer. The exonic and intronic DNA methylation has also been linked with aberrant gene expression in cancer. Recent studies have reported that genes playing an important role in the cell cycle, cell proliferation, apoptosis, and autophagy are sensitive to m6A status. These examples provide a glimpse of epigenetic modifications that are involved in different hallmarks of cancer.
Chemical modifications of nucleotide bases control the cellular fate by regulating biological processes including genomic imprinting, X-chromosome inactivation, repression of transposable elements, aging, and carcinogenesis. One of the most abundant chemical modifications is methylation that occurs at the DNA and RNA level. DNA methylation occurs at 5’ cytosine to guanosine (5’CpG) and shown to regulate the gene and non-coding RNA expressions such as microRNA (miRNA), long intergenic non-coding RNA (lncRNA), and circular RNA (circRNA). RNA methylation occurs at the N6 position of adenosine and is shown to influence mRNA, miRNA, lncRNA, and circRNA. While DNA cytosine methylation is very well studied and is considered as primary source of epigenetic modification, RNA adenosine methylation is a more recent addition to the field of epigenetics. Recent discoveries that both these modifications are essential for preventing aberrant activation of intracellular molecules that might result in disease conditions has attracted a lot of interest in targeting them therapeutically to treat cancer. However, the association between DNA and RNA methylation is still superficial, and a deep exploration toward the fundamental requirements for these essential epigenetic marks will provide a clear perspective on their converging and synergistic roles.
Dynamic structural changes are being introduced continuously in the DNA and RNA of all living cells through chemical alterations due to exposure to exogenous sources, or through endogenous metabolic pathways. DNA/RNA modifications through methylation are considered major sources of these changes. However, our current knowledge on the extent of methylation levels, its genomic distribution and the intricate interplay between DNA and RNA methylation specifically in context of cancer. In this special issue, we are inviting articles that address the intricate interplay between DNA and RNA methylation on the synthesis and function of critical genes and its implications particularly in the context of cancer.
For DNA methylation, DNMTs act as writers, TET as an eraser, and Zinc finger proteins as a reader. Similarly, for RNA methylation, METTL3/14, WTAP act as writer, FTO, and ALKBH5 as an eraser, and YTHDF proteins act as a reader. Differential promoter DNA methylation is associated with cancer progression and can have biomarker ability. For example, hypermethylation of tumor suppresser genes such as TFPI2, SOX17, and GATA4 and hypomethylation of oncogenes such as SPP1, AIM2, and PTHLH can act as biomarker for oral cancer. The exonic and intronic DNA methylation has also been linked with aberrant gene expression in cancer. Recent studies have reported that genes playing an important role in the cell cycle, cell proliferation, apoptosis, and autophagy are sensitive to m6A status. These examples provide a glimpse of epigenetic modifications that are involved in different hallmarks of cancer.
Chemical modifications of nucleotide bases control the cellular fate by regulating biological processes including genomic imprinting, X-chromosome inactivation, repression of transposable elements, aging, and carcinogenesis. One of the most abundant chemical modifications is methylation that occurs at the DNA and RNA level. DNA methylation occurs at 5’ cytosine to guanosine (5’CpG) and shown to regulate the gene and non-coding RNA expressions such as microRNA (miRNA), long intergenic non-coding RNA (lncRNA), and circular RNA (circRNA). RNA methylation occurs at the N6 position of adenosine and is shown to influence mRNA, miRNA, lncRNA, and circRNA. While DNA cytosine methylation is very well studied and is considered as primary source of epigenetic modification, RNA adenosine methylation is a more recent addition to the field of epigenetics. Recent discoveries that both these modifications are essential for preventing aberrant activation of intracellular molecules that might result in disease conditions has attracted a lot of interest in targeting them therapeutically to treat cancer. However, the association between DNA and RNA methylation is still superficial, and a deep exploration toward the fundamental requirements for these essential epigenetic marks will provide a clear perspective on their converging and synergistic roles.
Dynamic structural changes are being introduced continuously in the DNA and RNA of all living cells through chemical alterations due to exposure to exogenous sources, or through endogenous metabolic pathways. DNA/RNA modifications through methylation are considered major sources of these changes. However, our current knowledge on the extent of methylation levels, its genomic distribution and the intricate interplay between DNA and RNA methylation specifically in context of cancer. In this special issue, we are inviting articles that address the intricate interplay between DNA and RNA methylation on the synthesis and function of critical genes and its implications particularly in the context of cancer.
