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. 2009 Sep 25;4(9):e7169.
doi: 10.1371/journal.pone.0007169.

Investigating the targets of MIR-15a and MIR-16-1 in patients with chronic lymphocytic leukemia (CLL)

Katy Hanlon  1 , Claudius E Rudin, Lorna W Harries
Affiliations

Investigating the targets of MIR-15a and MIR-16-1 in patients with chronic lymphocytic leukemia (CLL)

Katy Hanlon et al. PLoS One. .

Abstract

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).

Methodology/principal findings: 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.

Significance: 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.

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Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Figure 1
Figure 1. Differentially expressed genes in patients with CLL and normal controls.
Bar graph representing the difference in relative gene expression in CLL patients compared with normal control patients. The dark grey bars above the x-axis represent genes that are significantly up-regulated in CLL patients compared with normal controls. Light grey bars below the x-axis represent genes that are significantly down-regulated in CLL patients when compared to normal controls. P-values; * represents <0.05, and ** represents <0.01
Figure 2
Figure 2. Significantly up-regulated genes in CLL patients with down-regulated miR-15a/16-1 expression.
Boxplot graphs representing the relative up-regulation of genes BAZ2A and RNF41 in CLL patients with down-regulated miR-15a/16-1 expression compared with CLL patients with normal miR-15a/16-1 expression.
Figure 3
Figure 3. Significantly down-regulated genes in CLL patients with down-regulated miR-15a/16-1 expression.
Boxplot graphs representing the relative down-regulation of genes RASSF5, MKK3 and LRIG1 in CLL patients with down-regulated miR-15a/16-1 expression compared with CLL patients with normal miR-15a/16-1 expression.
See this image and copyright information in PMC

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