Role of MicroRNA-146a in normal and malignant hematopoietic stem cell function

Regulation of hematopoiesis is controlled by microRNAs (miRNAs). In this review, we focus on miR-146a, and its role in regulating normal and malignant hematopoiesis. miR-146a is a negative regulator of immune cell activation by repressing two targets, TRAF6 and IRAK1. Genetic deletion of miR-146a confirmed a role of miR-146a during innate immune signaling as well as for hematopoietic stem cell function. miR-146a is also implicated in the pathogenesis of human myelodysplastic syndromes (MDSs) as it is located within a commonly deleted region on chromosome 5, and miR-146a-deficient mice exhibit features of an MDS-like disease. With new insight into miR-146a through genetic and expression analyses, we highlight and discuss the recent advances in the understanding of miR-146a in physiological hematopoiesis during steady-state and inflammation, as well as in MDS. ; © 2014 Zhao and Starczynowski. Received: 20 May 2014; Paper pending published: 03 June 2014; Accepted: 24 June 2014; Published online: 09 July 2014. Edited by: Ryan Michael O'Connell, University of Utah, USA. Reviewed by: Edward K. L. Chan, University of Florida, USA. Stefan Muljo, National Institute of Health – National Institute of Allergy and Infectious Diseases, USA. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. Jimmy L. Zhao would like to thank David Baltimore for mentorship and guidance regarding miRNA and NF-κB biology. The work was supported by a National Research Service Award (F30HL110691) and UCLA-Caltech Medical Scientist Training Program from the National Institutes of Health (Jimmy L. Zhao). Daniel T. Starczynowski is supported by Cincinnati Children's ...