NDLI: Oncomir miR-125b regulates hematopoiesis by targeting the gene Lin28A

Content Provider	PubMed Central
Author	Chaudhuri, Aadel A. So, Alex Yick-lun Mehta, Arnav Minisandram, Aarathi Sinha, Nikita Jonsson, Vanessa D. Rao, Dinesh S. O'connell, Ryan M. Baltimore, David
Abstract	MicroRNA-125b (miR-125b) is up-regulated in patients with leukemia. Overexpression of miR-125b alone in mice causes a very aggressive, transplantable myeloid leukemia. Before leukemia, these mice do not display elevation of white blood cells in the spleen or bone marrow; rather, the hematopoietic compartment shows lineage-skewing, with myeloid cell numbers dramatically increased and B-cell numbers severely diminished. miR-125b exerts this effect by up-regulating the number of common myeloid progenitors while inhibiting development of pre-B cells. We applied a miR-125b sponge loss of function system in vivo to show that miR-125b physiologically regulates hematopoietic development. Investigating the mechanism by which miR-125b regulates hematopoiesis, we found that, among a panel of candidate targets, the mRNA for Lin28A, an induced pluripotent stem cell gene, was most repressed by miR-125b in mouse hematopoietic stem and progenitor cells. Overexpressing Lin28A in the mouse hematopoietic system mimicked the phenotype observed on inhibiting miR-125b function, leading to a decrease in hematopoietic output. Relevant to the miR-125b overexpression phenotype, we also found that knockdown of Lin28A led to hematopoietic lineage-skewing, with increased myeloid and decreased B-cell numbers. Thus, the miR-125b target Lin28A is an important regulator of hematopoiesis and a primary target of miR-125b in the hematopoietic system.
Related Links	http://dx.doi.org/10.1073/pnas.1200677109
Ending Page	4238
Page Count	6
Starting Page	4233
File Format	PDF
ISSN	00278424
e-ISSN	10916490
Journal	Proceedings of the National Academy of Sciences of the United States of America
Issue Number	11
Volume Number	109
Language	English
Publisher	National Academy of Sciences
Publisher Date	2012-03-13
Access Restriction	Open
Rights Holder	National Academy of Sciences
Subject Keyword	General Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

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