Allelic methylation levels of the noncoding VTRNA2-1 located on chromosome 5q31.1 predict outcome in AML

Abstract

Deletions of chromosome 5q are associated with poor outcomes in acute myeloid leukemia (AML) suggesting the presence of tumor suppressor(s) at the locus. However, definitive identification of putative tumor suppressor genes remains controversial. Here we show that a 106-nucleotide noncoding RNA vault RNA2-1 (vtRNA2-1), previously misannotated as miR886, could potentially play a role in the biology and prognosis of AML. vtRNA2-1 is transcribed by polymerase III and is monoallelically methylated in 75% of healthy individuals whereas the remaining 25% of the population have biallelic hypomethylation. AML patients without methylation of VTRNA2-1 have a considerably better outcome than those with monoallelic or biallelic methylation (n ‫؍‬ 101, P ‫؍‬ .001). We show that methylation is inversely correlated with vtRNA2-1 expression, and that 5-azanucleosides induce vtRNA2-1 and down-regulate the phosphorylated RNA-dependent protein kinase (pPKR), whose activity has been shown to be modulated by vtRNA2-1. Because pPKR promotes cell survival in AML, the data are consistent with vtRNA2-1 being a tumor suppressor in AML. This is the first study to show that vtRNA2-1 might play a significant role in AML, that it is either mono-or biallelically expressed in the blood cells of healthy individuals, and that its methylation state predicts outcome in AML. (Blood. 2012; 119(1):206-216)

Reprogramming of the human intestinal epigenome by surgical tissue transposition

“…2C) or unmethylated (Supplemental Fig. 2D) across various tissues of different individuals but never fully methylated (Treppendahl et al 2012). The increase of methylation in this locus thus appears to be an effect of the drastic changes in the local tissue environment of the intestinal epithelial cells in the neobladder, rather than an artifact of sample heterogeneity.…”

c-Myc suppresses microRNA-29b to promote tumor aggressiveness and poor outcomes in non-small cell lung cancer by targeting FHIT

“…The bisulfitetreated in vitro methylated DNA was included in each run to serve as the 100% methylated reference for calculating the relative methylation percentages of the DNA samples based on the relative 2 (− ΔΔ C t ) quantitation approach. 40,41 Samples were considered to show positive methylation when the percentage of methylation was over 50%, and a finding of o 50% was considered as 'negative'.…”

Non-coding RNAs as direct and indirect modulators of epigenetic regulation

“…First, genomic loci producing non-coding transcripts are subject to epigenetic regulation similar to that of protein-coding genes. [38][39][40][41][42] Therefore, as with coding genes, environmental influences can lead to changes in their expression and to functional disturbances. We can include in this category the transcription of lncRNAs designated as "signals," 12 as these are examples of activity-dependent, sequence-independent changes in gene expression.…”