The down-regulation of miR-125b in chronic lymphocytic leukemias leads to metabolic adaptation of cells to a transformed state.
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.
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
Esmerina
E
Tili
Jean-Jacques
JJ
Michaille
Zhenghua
Z
Luo
Stefano
S
Volinia
Laura Z
LZ
Rassenti
Thomas J
TJ
Kipps
Carlo M
CM
Croce
D001402:B-Lymphocytes / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D015153:Blotting, Western; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D002478:Cells, Cultured; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D055432:Metabolomics; D035683:MicroRNAs / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction
D014408:Biomarkers, Tumor; C531888:MIRN125 microRNA, human; D035683:MicroRNAs; D012333:RNA, Messenger