MicroRNA dysregulation in B-cell non-Hodgkin lymphoma

Abstract

Emilia L Lim,1 Marco A Marra1,21Canada’s Michael Smith Genome Sciences Centre, BC Cancer Agency, Vancouver, BC, Canada; 2Department of Medical Genetics, University of British Columbia, Vancouver, BC, CanadaAbstract: B-cell non-Hodgkin lymphomas (NHLs) are lymphoproliferative disorders that can arise at different stages of B-cell development. Even though molecular classification of NHL has allowed for more accurate recognition of distinct aggressive lymphoma subtypes, many patients still fail to respond to standard therapy. As such, there is a need to identify biomarkers and therapeutic targets that can lead to more specific treatments for each NHL patient's disease. MicroRNAs (miRNAs) are small, 17–25 nt RNA molecules that regulate gene expression at the posttranscriptional level. miRNA expression and function is often coordinately dysregulated in NHL, and consequently results in each NHL disease type harboring a distinct miRNA expression signature. miRNA dysregulation may be a consequence of several mechanisms, ranging from dysregulation of the DNA sequences encoding the miRNA to transcriptional regulation of miRNA loci, to dysregulation of the miRNA biogenesis pathway or dysregulation of messenger RNA (mRNA) targets. This coordinated dysregulation of miRNA expression systematically results in the activation of several oncogenic pathways, and consequently the reprogramming of B-cell NHL transcriptomes. The widespread dysregulation of miRNAs suggests that miRNAs may be used as a diagnostic and prognostic tool, and also as actionable drug targets. In this review, we summarize the miRNA profiles of the most common B-cell NHLs, discuss the causes and consequences of miRNA dysregulation, and consider the prospects of miRNA-based biomarkers and therapeutic targets in NHL.Keywords: miRNA, non-Hodgkin lymphoma, dysregulation, therapy