Critical role of microRNAs in chronic lymphocytic leukemia: overexpression of the oncogene PLAG1 by deregulated miRNAs.

MicroRNAs (miRNAs) are small, gene encoded RNAs which are able to influence gene expression in binding to the 3'UTR of mRNAs. Compared to healthy tissues, the global expression of miRNAs in cancerous tissue is frequently down-regulated. Likewise in chronic lymphocytic leukemia (CLL), down-regulation of several miRNAs has been reported. Analysis of miRNA promoters for epigenetic modifications revealed a stronger methylation of down-regulated miRNAs in CLL. To date, several target genes affected by deregulated miRNAs have been identified that have impact on CLL pathogenesis. The best-described consequence of miRNA deregulation is for miRNA-15/16 cluster deletion, which is frequently down-regulated in a subgroup of patients with CLL carrying 13q14 deletion. So far, models for miRNA deregulation have addressed just single miRNAs. For assessment of complete miRNA deregulation, further evaluation of the results from microarray studies is needed. Previously we identified the oncogene PLAG1, whose expression is affected by various miRNAs deregulated in CLL. The involvement of miRNAs in PLAG1 expression was shown to be relevant in pleomorphic adenomas of the salivary gland, too. As PLAG1 is highly overexpressed, and its target genes appear to be deregulated in CLL, e.g. BCL-2, PLAG1 is a putative new relevant oncogene involved in the pathogenesis of CLL.