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Immunoglobulin Gene Sequence Analysis In Chronic Lymphocytic Leukemia: From Patient Material To Sequence Interpretation
Published on: November 26, 2018
Investigating the targets of MIR-15a and MIR-16-1 in patients with chronic lymphocytic leukemia (CLL)
Katy Hanlon1, Claudius E Rudin, Lorna W Harries
1Department of Haematology, Royal Devon and Exeter NHS Foundation Trust, Exeter, Devon, United Kingdom.
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.
Insights
MicroRNAs (miRNAs) are key regulators in cancer. Down-regulation of MIR-15a/16-1 in chronic lymphocytic leukemia (CLL) affects specific target genes, potentially driving tumorigenesis.
Area of Science:
- Molecular Biology
- Genetics
- Oncology
Background:
- MicroRNAs (miRNAs) are noncoding RNAs regulating gene expression.
- miRNA deregulation is implicated in human tumorigenesis.
- MIR-15a/16-1 cluster (13q14) is frequently down-regulated in chronic lymphocytic leukemia (CLL).
Purpose of the Study:
- To investigate the expression of MIR-15a/16-1 and its target genes in CLL.
- To identify specific genes regulated by the MIR-15a/16-1 cluster in CLL patients.
Main Methods:
- Gene expression profiling of MIR-15a/16-1 and 92 predicted target genes.
- Comparison between CLL patients and normal controls.
- Statistical analysis to identify deregulated genes.
Main Results:
- 35 genes were found to be deregulated in CLL patients.
- Five genes were identified as specific targets of the MIR-15a/16-1 cluster.
- Two genes (BAZ2A, RNF41) were significantly up-regulated, and three (RASSF5, MKK3, LRIG1) were significantly down-regulated in CLL with low MIR-15a/16-1 expression.
Conclusions:
- Identified genes may be direct or indirect targets of MIR-15a/16-1.
- These target genes are potential candidates for involvement in CLL tumorigenesis.
- MIR-15a/16-1 and its targets may play a significant role in the etiology of CLL.

