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

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.

S-Adenosylmethionine Inhibits Colorectal Cancer Cell Migration through Mirna-Mediated Targeting of Notch Signaling Pathway

“…It plays a primary role in cellular metabolism and represents the major methyl donor required in numerous methylation reactions [ 55 , 56 , 57 ]. Notably, AdoMet has been found to regulate the expression of miRNAs and lncRNAs through epigenetic mechanisms [ 35 ]. Recently, the effect of AdoMet on miRNA expression profile has been evaluated in breast [ 32 , 33 ] and in head and neck cancer [ 34 ], providing evidence that the ability of AdoMet to inhibit cell proliferation and migration, as well as to induce apoptosis in these tumor cells, is mediated by miRNAs.…”

“…More and more evidence has also shown that the epigenetic modulation of miRNAs involved in oncogenic functions represents one of the main mechanisms underlying the anticancer activity of AdoMet. The regulation of miRNA’s expression profile by AdoMet has been recently evaluated in breast and in head and neck cancer cells, suggesting that the ability of this natural compound to inhibit proliferation and cell migration, as well as to induce apoptosis in these tumor cells, is mediated by miRNAs [ 32 , 33 , 34 , 35 ].…”

S-Adenosylmethionine Increases the Sensitivity of Human Colorectal Cancer Cells to 5-Fluorouracil by Inhibiting P-Glycoprotein Expression and NF-κB Activation

“…The potential of AdoMet for cancer prevention has been widely investigated [13,14,22] and much evidence in recent years has highlighted this naturally-occurring multifunctional sulfonium compound as a promising chemosensitizing agent in various cancer types [8][9][10][11][12][13][14]. Interestingly, AdoMet is one of the most widely studied epigenetic regulators and a welldocumented modulator of noncoding RNAs involved in oncogenic functions [35][36][37][38]. The development of combination therapy with natural compounds able to synergize with chemotherapy drugs without causing significant toxic side-effects may represent a promising approach to increase 5-FU sensitivity and prevent drug resistance in CRC cells.…”

S-Adenosylmethionine, a Promising Antitumor Agent in Oral and Laryngeal Cancer

“…The antimetastatic properties of AdoMet have been well-documented in different types of human cancers, and the underlying mechanisms ranging from epigenetic regulation of genes responsible for cell migration and invasion [33][34][35][36] to the modulation of specific microRNAs (miRNAs) [59,62,63], have been elucidated. In OLSCC, AdoMet inhibits the migration and invasion of Cal-33 and JHU-SCC-011 cells by downregulating the expression of MMP2 and MMP9, two metalloproteinases involved in the degradation of the basement membrane and extracellular matrix.…”

“…More and more evidence has shown that epigenetic modulation of the level of noncoding RNA involved in oncogenic functions represents one of the mechanisms underlying the anticancer activity of AdoMet. Noncoding RNAs, especially miRNAs, have a significant role in carcinogenesis of head and neck cancers, acting both as oncogenes to promote cancer development and invasion and as tumor suppressors by participating in the modulation of cell proliferation, differentiation, migration, and invasion [63]. Notably, the role of miRNAs as biomarkers in HNSCC has recently been evidenced [67].…”