Methylation of Human MicroRNA Genes in Normal and Neoplastic Cells

Epigenetic regulation mechanisms of microRNA expression

“…The frequency of human miRNA gene methylation is nearly one order of magnitude higher than that of the protein-encoding genes (44). To further shed light on this fact, we depicted the genomic distribution of human miRNAs (obtained from miRbase v21) (45) throughout the chromosomes and merged this chromosome map with the CpG island genomic density using karyoploteR (46) ( Figure 1A).…”

A new perspective on neural tube defects: Folic acid and microRNA misexpression

“…RA pushes cells toward a neural fate, inhibits proliferation, and attenuates Fgf8 expression in the neuroepithelium. RA was also found to increase miRNA expression in Hl-60 myeloid leukemia cells (Weber et al, 2007), increase miR-34a expression in SK-N-AS neuroblastoma cells (Kim et al, 2003), and a recent study in a spina bifida rat model showed that RA not only led to increased cell death but was responsible for the downregulation of miR-9/9*, miR-124a, and miR-125b as well as a decrease in the expression of Bcl-2 and p53 in the affected spinal cords. This link between RA, spina bifida, and miRNA downregulation further strengthens the likelihood that misexpression of miRNAs plays a part in the development of NTDs (Fig.…”

“…miRNAs have been shown to be a driving force in embryonic development in multiple species (such as zebrafish, xenopus, and mouse) (Foshay and Gallicano, 2009;Leucht et al, 2008) and have distinct expression patterns within the developing brain and CNS (Bak et al, 2008). Because of the prediction that miRNAs are highly regulated by genomic methylation, it is a logical question to ask if alteration in methylgroup availability and methylation patterns affects expression of miRNAs (Han et al, 2007;Weber et al, 2007). Recent evidence supports this line of reasoning.…”

“…Because so many current mouse models display extreme phenotypes or embryonic lethality, and heterozygotes are usually unaffected, mutations in genes, especially null mutations, do not seem sufficient to explain NTDs (Bell et al, 2003;Bulgakov et al, 2004;Finnell et al, 2002;Friedman and Kaestrer, 2006;Hatakeyama et al, 2004;Hirata et al, 2001;Mathers, 2005;Nagai et al, 2000;Pierani et al, 2001;Sahara et al, 2007;Tachibana et al, 2002;Xu et al, 1999). miRNAs may offer a more subtle deregulation, and there is enough evidence that miRNA genes are under regulation by methylation to add plausibility to the idea (Bak et al, 2008;Han et al, 2007;Lujambio et al, 2007;Weber et al, 2007). A better understanding of how folic acid deficiency may contribute to misexpression of miRNAs and whether this can lead to NTDs will broaden our knowledge of CNS development as well as possibly lead us to new treatments to further decrease their incidence.…”

Inflammatory memories: Is epigenetics the missing link to persistent stromal cell activation in rheumatoid arthritis?

“…The global hypomethylated state of DNA in RASFs would therefore mainly affect non-regulatory sequences such as retrotransposons and repetitive sequences, coding DNA and intergenic DNA. Intriguingly, around 50% of the genes coding for microRNAs have been found to be controlled by DNA methylation, and in tumor cells aberrant hyper-as well as hypomethylation of microRNA genes is detectable [43]. MicroRNAs are small non-coding RNAs that modulate gene expression by degradation of target mRNA or by inhibition of protein translation.…”