Folate and microRNA: Bidirectional interactions

Abstract

Low folate status is linked to increased risk of a number of conditions, including developmental disorders, some cancers, neurodegenerative and cardiovascular diseases. Some of the mechanisms of these associations are known, but much remains to be elucidated. Aberrant microRNA (miRNA) profiles are also signatures of these conditions, and as such, the association between folate status and miRNA are now being investigated. Potential associations are bidirectional, with miRNA linked to regulation of folate-mediated pathways, and folate linked to modulation of miRNA expression. miRNA are short non-coding RNA, involved in post-transcriptional regulation of gene expression via complementary binding to mRNA. Evidence is emerging that links folate levels to the regulation of miRNA levels, and miRNA to the regulation of the expression of enzymes involved in folate mediated one carbon metabolism. One carbon metabolism is the source of methyl groups for methylation reactions, including DNA methylation and is important in DNA synthesis and repair. miRNA may be modulated by DNA methylation and other epigenetic mechanisms directly, or indirectly via modulation of upstream signalling pathways. As such, there may be bi-directional associations between folate status and miRNA profiles. miRNA may also act as biomarkers for diagnosis or prognosis of conditions associated with folate status.

Keywords: Cancer; Development; Folate; Folic acid; Neural tube defects; microRNA.