%0 Journal Article
%T The emerging role of MIR-146A in the control of hematopoiesis, immune function and cancer
%A Catherine Labbaye
%A Ugo Testa
%J Journal of Hematology & Oncology
%D 2012
%I BioMed Central
%R 10.1186/1756-8722-5-13
%X Most vertebrates have two copies of the gene encoding miR-146, miR-146a and miR-146b, located at the level of different chromosomes, 5 and 10, respectively, within different genes. The structural differences of these two miRNAs are very limited since they differ in their mature sequences by just two nucleotides located at the 3' end. In spite these great structural similarities, miR-146a and miR-146b do not seem to be redundant in their biologic activity, as suggested by the observation that they may have a different post-transcritpional processing mechanism: thus, following lipopolysaccharide stimulation the transcription of both miR-146a and miR-146b is stimulated, but only mature miR-146a is produced [1].MiR-146a was initially discovered during a systematic study aiming to identify miRNAs that play a potentially important role in the innate immune response to microbial infection [2]. Particularly, expression profiling of 200 miRNAs in human monocytes revealed that some miRNAs, including miR-146a and miR-155, are strongly upmodulated following challenging of these cells with bacterial endotoxin [2]. The analysis of the miR-146a promoter provided evidence that miR-146a is a NF-kappaB-dependent gene [2]. miR-146a was predicted to base-pair with sequences in the 3' UTR of the TNF receptor-associated factor 6 (TRAF6) and IL-1 receptor-associated kinase 1 (IRAK1) genes (Table 1). Both these two genes encode key adaptor molecules downstream of Toll-like and cytokine receptors.Studies carried out in vesicular stomatitis virus (VSV)-infected macrophages showed that macrophage infarction induced a marked upmodulation of miR-146a that was shown to target IRAK2, in addition to the previously reported TRAF6 and IRAK1 [3].The study of human lung alveolar epithelial cells have led to the identification of additional miR-146a targets involved in the control of innate immunity. In fact, Perry and coworkers showed that exposure of human lung alveolar epithelial cells to IL-1¦Â resu
%U http://www.jhoonline.org/content/5/1/13