%0 Journal Article
%T The Role of miRNA in Haematological Malignancy
%A Stephanie Gounaris-Shannon
%A Timothy Chevassut
%J Bone Marrow Research
%D 2013
%I Hindawi Publishing Corporation
%R 10.1155/2013/269107
%X Currently, there are over 1,800 annotated human miRNAs, many of which have tissue-specific expression. Numerous studies have highlighted their role in haematopoietic differentiation and proliferation, acting as master regulators of haematopoietic stem cell function. Aberrant expression of miRNAs has been observed in haematological cancers, exhibiting unique expression signatures in comparison to normal counterparts. Functional and target analyses as well as animal models have attempted to annotate how different miRNA may contribute to the pathophysiology of these malignancies from modulating cancer associated genes, functioning directly as oncogenes or tumour suppressor genes or acting as bystanders or regulators of the epigenetic mechanisms in cancer. miRNAs have also been shown to play a role in modulating drug resistance and determining prognosis between the various subtypes of blood cancers. This review discusses the important role that miRNAs play in haematological malignancies by exploring associations that exist between the two and trying to examine evidence of causality to support the tantalising possibility that miRNAs might serve as therapeutic targets in blood cancers. 1. Introduction The haematological malignancies are a diverse group of neoplastic diseases. They are representing the fifth most common cancer in the UK and are among the twenty most common causes of cancer deaths in the UK [1]. A combination of clinical, cytogenetic, and genetic features and immunophenotype and cell morphology are used to stratify each of the haematological cancers further into subtypes [2]. Tumourigenesis has long been attributed to the alteration of oncogenes and tumour suppressor genes [3]. However, the discovery of non-protein-coding RNA, such as microRNAs (miRNAs) and their possible associations with cancer, has certified suspicions that tumour pathogenicity is far more complex than the simple deregulation of protein-coding genes and warrants further investigation. There are currently 1,862 miRNAs annotated in humans [4], most of which are evolutionarily conserved. miRNAs are 20¨C22 nucleotide transcripts in their mature form and function to inhibit gene expression via negative regulation of mRNA at a posttranscriptional level [5] (Figure 1). In vivo mice studies have illustrated that disruption of miRNA biogenesis through depletion of Dicer leads to embryological and developmental arrest and subsequent incompatibility with life [6]. miRNAs have since been demonstrated to be vital in other essential biological processes such as metabolism [5, 7],
%U http://www.hindawi.com/journals/bmr/2013/269107/