Mutual Correlation between Non-Coding RNA and S-Adenosylmethionine in Human Cancer: Roles and Therapeutic Opportunities

SIMPLE SUMMARY: Non-coding RNAs and S-adenosylmethionine, the methyl donor required in all epigenetic methylation reactions, have emerged in recent years as crucial players in the modulation of gene expression in different types of human cancers. This review summarizes the most recent findings on reciprocal regulation between AdoMet and non-coding RNAs. AdoMet was found to exert anticancer activity through epigenetic regulation of non-coding RNAs, including microRNAs, long non-coding RNAs and circular RNAs. On the other hand, several microRNAs and long non-coding RNAs have been reported to display regulatory effects on the expression of genes involved in AdoMet synthesis and metabolism. Increasing knowledge on the relationship between AdoMet and non-coding RNAs will provide insights for further development of diagnostic and therapeutic strategies for cancer treatments. ABSTRACT: Epigenetics includes modifications in DNA methylation, histone and chromatin structure, and expression of non-coding RNAs (ncRNAs), especially microRNAs (miRNAs) and long non-coding RNAs (lncRNAs). Knowledge of the relationships between S-adenosylmethionine (AdoMet or SAM), the universal methyl donor for all epigenetic methylation reactions and miRNAs or lncRNAs in human cancer may provide helpful insights for the development of new end more effective anticancer therapeutic approaches. In recent literature, a complex network of mutual interconnections between AdoMet and miRNAs or lncRNAs has been reported and discussed. Indeed, ncRNAs expression may be regulated by epigenetic mechanisms such as DNA and RNA methylation and histone modifications. On the other hand, miRNAs or lncRNAs may influence the epigenetic apparatus by modulating the expression of its enzymatic components at the post-transcriptional level. Understanding epigenetic mechanisms, such as dysregulation of miRNAs/lncRNAs and DNA methylation, has become of central importance in modern research. This review summarizes the recent findings on the mechanisms by which AdoMet and miRNA/lncRNA exert their bioactivity, providing new insights to develop innovative and more efficient anticancer strategies based on the interactions between these epigenetic modulators.