Investigating the targets of MIR-15a and MIR-16-1 in patients with chronic lymphocytic leukemia (CLL).
BACKGROUND
MicroRNAs (miRNAs) are short, noncoding RNAs that regulate the expression of multiple target genes. Deregulation of miRNAs is common in human tumorigenesis. The miRNAs, MIR-15a/16-1, at chromosome band 13q14 are down-regulated in the majority of patients with chronic lymphocytic leukaemia (CLL).


RESULTS
We have measured the expression of MIR-15a/16-1, and 92 computationally-predicted MIR-15a/16-1 target genes in CLL patients and in normal controls. We identified 35 genes that are deregulated in CLL patients, 5 of which appear to be specific targets of the MIR-15a/16-1 cluster. These targets included 2 genes (BAZ2A and RNF41) that were significantly up-regulated (p<0.05) and 3 genes (RASSF5, MKK3 and LRIG1) that were significantly down-regulated (p<0.05) in CLL patients with down-regulated MIR-15a/16-1 expression.


CONCLUSIONS
The genes identified here as being subject to MIR-15a/16-1 regulation could represent direct or indirect targets of these miRNAs. Many of these are good biological candidates for involvement in tumorigenesis and as such, may be important in the aetiology of CLL.
Department of Haematology, Royal Devon and Exeter NHS Foundation Trust, Exeter, Devon, United Kingdom.
Katy
K
Hanlon
Claudius E
CE
Rudin
Lorna W
LW
Harries
D002875:Chromosomes / Q000648:ultrastructure; D002882:Chromosomes, Human, Pair 13; D019295:Computational Biology / Q000379:methods; D015536:Down-Regulation; D020869:Gene Expression Profiling; D015973:Gene Expression Regulation, Leukemic; D006801:Humans; D016130:Immunophenotyping; D017404:In Situ Hybridization, Fluorescence; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000235:genetics* / Q000378:metabolism*; D035683:MicroRNAs / Q000096:biosynthesis*; D012313:RNA / Q000378:metabolism
C505361:MIRN15 microRNA, human; C505362:MIRN16 microRNA, human; D035683:MicroRNAs; D012313:RNA