The interactions between DNA methylation machinery and long non-coding RNAs in tumor progression and drug resistance

DNA methylation is one of the main epigenetic mechanisms in cancer development and progression. Aberrant DNA methylation of CpG islands within promoter regions contributes to the dysregulation of various tumor suppressors and oncogenes; this leads to the appearance of malignant features, including rapid proliferation, metastasis, stemness, and drug resistance. The discovery of two important protein families, DNA methyl-transferases (DNMTs) and Ten-eleven translocation (TET) dioxygenases, respectively, which are responsible for deregulated transcription of genes that play pivotal roles in tumorigenesis, led to further understanding of DNA methylation-related pathways. But how these enzymes can target specific genes in different malignancies; recent studies have highlighted the considerable role of Long Non-coding RNAs (LncRNAs). LncRNAs recruit these enzymes to promoter regions of genes and mediate their functions, showing great potential as therapeutic agents targeting the epigenetic regulation of various genes. Considering the importance of combining the current treatment methods, especially chemotherapies, with DNA methylation inhibitors in improving patients' out-comes, this review aimed to summarize the recent findings about the interaction between DNA methylation machinery and LncRNAs in regulating genes involved in tumorigenesis and drug resistance. So, these studies could provide insights toward developing novel strategies for cancer-targeted therapy.

Automated summary

DNA methylation is an important mechanism in cancer development and progression. Aberrant methylation of CpG islands within promoter regions leads to dysregulation of tumor suppressors and oncogenes, resulting in malignant features. Recent studies have highlighted the role of LncRNAs in recruiting enzymes involved in methylation and mediating their functions. This opens up potential therapeutic strategies for targeted cancer therapy.