6533b822fe1ef96bd127d950

RESEARCH PRODUCT

The down-regulation of miR-125b in chronic lymphocytic leukemias leads to metabolic adaptation of cells to a transformed state

Zhenghua LuoStefano VoliniaLaura Z. RassentiCarlo M. CroceThomas J. KippsEsmerina TiliJean-jacques MichailleJean-jacques Michaille

subject

Blotting WesternImmunologyBiologyReal-Time Polymerase Chain ReactionBiochemistryNODownregulation and upregulationmicroRNABiomarkers TumorHumansMetabolomicsRNA MessengerPsychological repressionCells CulturedCell ProliferationOligonucleotide Array Sequence AnalysisRegulation of gene expressionB-LymphocytesLymphoid NeoplasiaReverse Transcriptase Polymerase Chain ReactionCell growthGene Expression ProfilingCell BiologyHematologyLeukemia Lymphocytic Chronic B-CellMolecular biologyGene Expression Regulation NeoplasticGene expression profilingMicroRNAsMetabolic pathwayCell Transformation NeoplasticChromosomal regionCancer research

description

AbstractMiR-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 also were observed in CLLs. We furthermore analyzed the expression of some of miR-125b–target transcripts that are potentially involved in the aforementioned 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 patients with CLL.

yearjournalcountryeditionlanguage
2012-09-27Blood
https://doi.org/10.1182/blood-2012-03-415737