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|Titolo:||The downregulation of miR-125b in chronic lymphocytic leukemias leads to metabolic adaptation of cells to a transformed state.|
|Autori interni:||VOLINIA, Stefano|
CROCE, Carlo Maria
|Data di pubblicazione:||2012|
|Abstract:||MiR-125b-1 maps at 11q24, a chromosomal region close to the epicenter of 11q23 deletions in chronic lymphocytic leukemias (CLLs). Our results establish that both aggressive and indolent CLL patients show reduced expression of miR-125b. Overexpression of miR-125b in CLL-derived cell lines resulted in the repression of many transcripts encoding enzymes implicated in cell metabolism. Metabolomics analyses showed that miR-125b overexpression modulated glucose, glutathione, lipid and glycerolipid metabolism. Changes on the same metabolic pathways were also observed in CLLs. We furthermore analyzed the expression of some of miR-125b-target transcripts that are potentially involved in the above metabolic pathways and defined a miR-125b-dependent CLL metabolism-related transcript signature. Thus, miR-125b acts as a master regulator for the adaptation of cell metabolism to a transformed state. MiR-125b and miR-125b-dependent metabolites therefore warrant further investigation as possible novel therapeutic approaches for CLLs.|
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