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Blood. 2012 Sep 27;120(13):2631-8. Epub 2012 Jun 21.

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

Author information

1
Department of Molecular Virology, Immunology and Medical Genetics, The Ohio State University Medical Center and Comprehensive Cancer Center, Columbus, OH 43210, USA. esmerina.tili@gmail.com

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 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.

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PMID:
22723551
PMCID:
PMC3460685
DOI:
10.1182/blood-2012-03-415737
[Indexed for MEDLINE]
Free PMC Article

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