Investigating the Targets of MIR-15a and MIR-16-1 in Patients with Chronic Lymphocytic Leukemia (CLL)

• Published in: PloS one Vol. 4; no. 9; p. e7169
• Main Authors: Hanlon, Katy, Rudin, Claudius E., Harries, Lorna W.
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 25.09.2009; Public Library of Science (PLoS)
• Subjects: Bone marrow; Cancer; Cell Biology/Gene Expression; Cell growth; Chromosomes; Chromosomes - ultrastructure; Chromosomes, Human, Pair 13; Chronic lymphocytic leukemia; Computational Biology - methods; Deregulation; Disease; Down-Regulation; Gene expression; Gene Expression Profiling; Gene Expression Regulation, Leukemic; Genes; Genetics and Genomics/Cancer Genetics; Growth factors; Hematology; Humans; Immunophenotyping; In Situ Hybridization, Fluorescence; Kinases; Leukemia; Leukemia, Lymphocytic, Chronic, B-Cell - genetics; Leukemia, Lymphocytic, Chronic, B-Cell - metabolism; Lymphatic leukemia; Medical prognosis; Medical research; MicroRNA; MicroRNAs; MicroRNAs - biosynthesis; miRNA; Molecular Biology/Post-Translational Regulation of Gene Expression; Patients; Predictive control; RNA - metabolism; Signal transduction; Studies; Tumorigenesis; United Kingdom > UK; United States > US
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0007169

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). 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. 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.