Phylogenetic Analysis Based On Glycolytic-enzymes

The amino-acid sequences of glycolytic enzymes were used to determine the evolutionary relationships between organisms. Glycolytic enzymes are suitable evolutionary chronometers, because they are ubiquitously present. Moreover, their evolution rate is sufficiently slow to enable their use for tracing overall patterns of evolution, but still fast enough to use them for the precise classification of closely related organisms. Our analysis has revealed several examples of horizontal gene transfer between organisms. Some of these transfers can be attributed to the endosymbiotic origin of plastids in plants and the subsequent migration of DNA from the prokaryotic genome of the organelle to the plant nucleus. However, other examples of putative gene transfer involve non-phototrophic organisms; in these latter cases other transfer mechanisms should be invoked. Some anomalies in phylogenetic trees remain so far unexplained. Metabolic constraints or additional functions for glycolytic enzymes may have influenced the direction and rate of evolution of glycolytic enzymes in some organisms

MiR-17-92 and miR-221/222 cluster members target KIT and ETV1 in human gastrointestinal stromal tumours

Background:Gastrointestinal stromal tumours (GIST) are characterised by high expression of KIT and ETV1, which cooperate in GIST oncogenesis. Our aim was to identify microRNAs that are deregulated in GIST, have a role in GIST pathogenesis, and could potentially be used as therapeutic tool.Methods:Differentially expressed microRNAs between primary GIST (n=50) and gastrointestinal leiomyosarcomas (GI-LMS, n=10) were determined using microarrays. Selected microRNA mimics were transfected into GIST-882 and GIST-T1 cell lines to study the effects of microRNA overexpression on GIST cells. Luciferase reporter assays were used to establish regulation of target genes by selected microRNAs.Results:MiR-17-92 and miR-221/222 cluster members were significantly (P<0.01) lower expressed in GIST vs GI-LMS and normal gastrointestinal control tissues. MiR-17/20a/222 overexpression in GIST cell lines severely inhibited cell proliferation, affected cell cycle progression, induced apoptosis and strongly downregulated protein and - to a lesser extent - mRNA levels of their predicted target genes KIT and ETV1. Luciferase reporter assays confirmed direct regulation of KIT and ETV1 by miR-222 and miR-17/20a, respectively.Conclusion:MicroRNAs that may have an essential role in GIST pathogenesis were identified, in particular miR-17/20a/222 that target KIT and ETV1. Delivering these microRNAs therapeutically could hold great potential for GIST management, especially in imatinib-resistant disease.British Journal of Cancer advance online publication, 22 August 2013; doi:10.1038/bjc.2013.483 www.bjcancer.com.status: publishe