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.

Plos One
|September 26, 2009
PubMed
Abstract

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.