PMID- 20933052
OWN - NLM
STAT- MEDLINE
DCOM- 20110310
LR  - 20110124
IS  - 1873-2399 (Electronic)
IS  - 0301-472X (Linking)
VI  - 39
IP  - 2
DP  - 2011 Feb
TI  - MicroRNA-146a disrupts hematopoietic differentiation and survival.
PG  - 167-178.e4
LID - 10.1016/j.exphem.2010.09.011 [doi]
AB  - OBJECTIVE: MicroRNAs (miRNAs) are short noncoding RNAs capable of exerting 
      dramatic effects by postranscriptionally regulating numerous messenger RNA 
      targets. Toll-like receptor-4 (TLR-4) activation by lipopolysaccharide (LPS) 
      induces the expression of three miRNAs in myeloid cells. The aim of this study 
      was to investigate the in vivo consequences of expressing one of the LPS-induced 
      miRNA, miR-146a, in bone marrow cells. MATERIAL AND METHODS: The role of miR-146a 
      in hematopoiesis was investigated by using retroviral infection and 
      overexpression of miR-146a in mouse hematopoietic stem/progenitor cells, followed 
      by bone marrow transplantations. RESULTS: miR-146a is mainly expressed in 
      primitive hematopoietic stem cells and T lymphocytes. Overexpression of miR-146a 
      in hematopoietic stem cells, followed by bone marrow transplantation, resulted in 
      a transient myeloid expansion, decreased erythropoiesis, and impaired 
      lymphopoiesis in select anatomical locations. Enforced expression of miR-146a 
      also impaired bone marrow reconstitution in recipient mice and reduced survival 
      of hematopoietic stem cells. CONCLUSIONS: Our results indicate that miR-146a, an 
      LPS-induced miRNA, regulates multiple aspects of hematopoietic differentiation 
      and survival. Furthermore, the consequences of miR-146a expression in 
      hematopoietic cells mimics some of the reported effects with acute LPS exposure.
CI  - Copyright (c) 2011 ISEH - Society for Hematology and Stem Cells. Published by 
      Elsevier Inc. All rights reserved.
FAU - Starczynowski, Daniel T
AU  - Starczynowski DT
AD  - British Columbia Cancer Agency Research Centre, 675 West 10th Avenue, Vancouver, 
      BC, Canada.
FAU - Kuchenbauer, Florian
AU  - Kuchenbauer F
FAU - Wegrzyn, Joanna
AU  - Wegrzyn J
FAU - Rouhi, Arefeh
AU  - Rouhi A
FAU - Petriv, Oleh
AU  - Petriv O
FAU - Hansen, Carl L
AU  - Hansen CL
FAU - Humphries, R Keith
AU  - Humphries RK
FAU - Karsan, Aly
AU  - Karsan A
LA  - eng
GR  - MOP 89976/Canadian Institutes of Health Research/Canada
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20101007
PL  - Netherlands
TA  - Exp Hematol
JT  - Experimental hematology
JID - 0402313
RN  - 0 (MicroRNAs)
RN  - 0 (Mirn146 microRNA, mouse)
SB  - IM
MH  - Animals
MH  - Base Sequence
MH  - Bone Marrow/metabolism
MH  - *Cell Differentiation
MH  - Cell Survival
MH  - Erythroid Cells/cytology/metabolism
MH  - Gene Expression Profiling
MH  - Hematopoiesis/genetics
MH  - Hematopoietic Stem Cells/*cytology/*metabolism
MH  - Lymphocytes/cytology/metabolism
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - MicroRNAs/genetics/*metabolism
MH  - Molecular Sequence Data
MH  - Up-Regulation
EDAT- 2010/10/12 06:00
MHDA- 2011/03/11 06:00
CRDT- 2010/10/12 06:00
PHST- 2010/07/10 00:00 [received]
PHST- 2010/09/15 00:00 [revised]
PHST- 2010/09/29 00:00 [accepted]
PHST- 2010/10/12 06:00 [entrez]
PHST- 2010/10/12 06:00 [pubmed]
PHST- 2011/03/11 06:00 [medline]
AID - S0301-472X(10)00492-3 [pii]
AID - 10.1016/j.exphem.2010.09.011 [doi]
PST - ppublish
SO  - Exp Hematol. 2011 Feb;39(2):167-178.e4. doi: 10.1016/j.exphem.2010.09.011. Epub 
      2010 Oct 7.