We performed literature search for research articles describing epigenetically regulated miRNAs in cancer and identified 45 studies that were published between 2006 and July 2010. The data from those papers is fragmented and methodologically heterogeneous and our work represents first systematic review towards to integration of diverse sets of information. We reviewed the methods used for detection of miRNA epigenetic regulation, which comprise bisulfite genomic sequencing PCR (BSP), bisulfite pyrosequencing, methylation specific PCR (MSP), combined bisulfite restriction analysis (COBRA), methylation sensitive single nucleotide primer extension (Ms-SNuPE), MassARRAY technique and some modifications of those methods. This integrative study revealed 122 miRNAs that were reported to be epigenetically regulated in 23 cancer types. Compared to protein coding genes, human oncomiRs showed an order of magnitude higher methylation frequency (13%; 122/940 known miRNAs). Nearly half, (45%; 55/122) epigenetically regulated miRNAs were associated with different cancer types, but other 55% (67/122) miRNAs were present in only one cancer type and therefore representing cancer-specific biomarker potential. The data integration revealed miRNA epigenomic hot spots on the chromosomes 1q, 7q, 11q, 14q and 19q. CpG island analysis of corresponding miRNA precursors (pre-miRNAs) revealed that 20% (26/133) of epigenetically regulated miRNA had a CpG island within the range of 5 kb upstream, among them 14% (19/133) of miRNAs resided within the CpG island. Our integrative survey and analyses revealed candidate cancer-specific miRNA epigenetic signatures which provide the basis for new therapeutic strategies in cancer by targeting the epigenetic regulation of miRNAs.
COBISS.SI-ID: 2837128
Marble trout (Salmo marmoratus) populate two geographically separated areas in the nothern and sothern parts of the Adriatic Sea drainage. Although morphologically similar, each population is distinguished by a different set of unrelated mitochondrial haplotypes, suggesting that they have evolved from different ancestors. Due to a possible discordance between mitochondrial and species phylogeny, we performed phylogenetic analysis based on 22 nuclear loci. The results inferred from Maximum-likelihood and Bayesian Inference analysis revealed that nothern and southern populations are closley related, forming a monophyletic group. This observation is concordant with the present marble trout classification, which considers both populations as conspecific. On the other hand, our findings are in marked contarst to those of previous mtDNA-based studies and highlight potential dangers of making phylogenetic inferences from mtDNA alone. Reasons for discordance between mtDNA and nDNA phylogeny are discussed with incomplete lineage sorting proposed as the most parsimonious explanation for mtDNA divergence in marble trout.
COBISS.SI-ID: 2848136
Obesity and metabolic syndrome results from a complex interaction between genetic and environmetal factors. In addition to brain-regulated processes, recent genome wide association studies have indicated that genes highly expressed in adipose tissue affect the distribution and function of fat and thus contribute to obesity. Using a stratified transcriptome gene enrichment approach we attempted to identify adipose tissue-specific obesity genes in the unique polygenic fat (F) mouse strain generated by selective breeding over 60 generations for divergent adiposity from a comparator lean (L) strain. To enrich for adipose tissue obesity genes a ˝snap-shot˝ pooled-sample transcriptome comparison of key fat depots and non adipose tissue (muscle, liver, kidney) was performed. Known obesity quantitative trait loci (QTL) information for the model allowed us to further filter genes for increased likelihood of being causal or secondary for obesity. This successfully identified several genes previously linked to obesity (C1qr1, and Np3r) as positional QTL candidate genes elevated specifically in F line adipose tissue.A number of novel obesity candidate genes were also identified (Thbs1, Ppp1rd, Tmepai, Trp53inp2, Ttc7b, Tuba1a, Fgf13, Fmr) that have inferred rolesin fat cell function. Quantitative microarray analysis was then applied to the most phenotypically divergent adipose depot after exaggerating F and L strain differences with chronic high fat feeding which revealed a dictinct gene expression profile of line, fat depot and diet-responsive inflammatory, angiogenic and metabolic pathaways. Selected candidate genes Npr3 and Thbs1, as well as Gys2, a non-QTL gene that otherwise passed our enrichment criteria were characterised, revealing novel functional effects consistent with a contribution to obesity. A focussed candidate gene enrichment strategy in the unique F and L model has identified novel adipose tissue-enriched genes contributing to obesity.
COBISS.SI-ID: 2943624