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

Aadel A. Chaudhuri, Alex Yick Lun So, Arnav Mehta, Aarathi Minisandram, Nikita Sinha, Vanessa D. Jonsson, Dinesh S. Rao, Ryan M. O'Connell, David Baltimore

Research output: Contribution to journalArticlepeer-review

124 Scopus citations

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 inhibitingmiR- 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.

Original languageEnglish
Pages (from-to)4233-4238
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume109
Issue number11
DOIs
StatePublished - Mar 13 2012

Keywords

  • Cancer
  • Lymphocyte
  • Myelogenous

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