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miR-126 Regulates Distinct Self-Renewal Outcomes in Normal and Malignant Hematopoietic Stem Cells.

Lechman, Eric R ; Gentner, Bernhard ; Ng, Stanley W K ; Schoof, Erwin M ; van Galen, Peter ; Kennedy, James A ; Nucera, Silvia ; Ciceri, Fabio ; Kaufmann, Kerstin B and Takayama, Naoya , et al. (2016) In Cancer Cell 29(2). p.214-228
Abstract
To investigate miRNA function in human acute myeloid leukemia (AML) stem cells (LSC), we generated a prognostic LSC-associated miRNA signature derived from functionally validated subpopulations of AML samples. For one signature miRNA, miR-126, high bioactivity aggregated all in vivo patient sample LSC activity into a single sorted population, tightly coupling miR-126 expression to LSC function. Through functional studies, miR-126 was found to restrain cell cycle progression, prevent differentiation, and increase self-renewal of primary LSC in vivo. Compared with prior results showing miR-126 regulation of normal hematopoietic stem cell (HSC) cycling, these functional stem effects are opposite between LSC and HSC. Combined transcriptome and... (More)
To investigate miRNA function in human acute myeloid leukemia (AML) stem cells (LSC), we generated a prognostic LSC-associated miRNA signature derived from functionally validated subpopulations of AML samples. For one signature miRNA, miR-126, high bioactivity aggregated all in vivo patient sample LSC activity into a single sorted population, tightly coupling miR-126 expression to LSC function. Through functional studies, miR-126 was found to restrain cell cycle progression, prevent differentiation, and increase self-renewal of primary LSC in vivo. Compared with prior results showing miR-126 regulation of normal hematopoietic stem cell (HSC) cycling, these functional stem effects are opposite between LSC and HSC. Combined transcriptome and proteome analysis demonstrates that miR-126 targets the PI3K/AKT/MTOR signaling pathway, preserving LSC quiescence and promoting chemotherapy resistance. (Less)
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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Cancer Cell
volume
29
issue
2
pages
214 - 228
publisher
Cell Press
external identifiers
  • pmid:26832662
  • scopus:84958635003
  • wos:000369739100013
  • pmid:26832662
ISSN
1878-3686
DOI
10.1016/j.ccell.2015.12.011
language
English
LU publication?
yes
id
e1407822-759c-46a3-af5a-ceed348f9e92 (old id 8829996)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/26832662?dopt=Abstract
date added to LUP
2016-04-04 07:13:33
date last changed
2022-03-23 00:48:58
@article{e1407822-759c-46a3-af5a-ceed348f9e92,
  abstract     = {{To investigate miRNA function in human acute myeloid leukemia (AML) stem cells (LSC), we generated a prognostic LSC-associated miRNA signature derived from functionally validated subpopulations of AML samples. For one signature miRNA, miR-126, high bioactivity aggregated all in vivo patient sample LSC activity into a single sorted population, tightly coupling miR-126 expression to LSC function. Through functional studies, miR-126 was found to restrain cell cycle progression, prevent differentiation, and increase self-renewal of primary LSC in vivo. Compared with prior results showing miR-126 regulation of normal hematopoietic stem cell (HSC) cycling, these functional stem effects are opposite between LSC and HSC. Combined transcriptome and proteome analysis demonstrates that miR-126 targets the PI3K/AKT/MTOR signaling pathway, preserving LSC quiescence and promoting chemotherapy resistance.}},
  author       = {{Lechman, Eric R and Gentner, Bernhard and Ng, Stanley W K and Schoof, Erwin M and van Galen, Peter and Kennedy, James A and Nucera, Silvia and Ciceri, Fabio and Kaufmann, Kerstin B and Takayama, Naoya and Dobson, Stephanie M and Trotman-Grant, Aaron and Krivdova, Gabriela and Elzinga, Janneke and Mitchell, Amanda and Nilsson, Björn and Hermans, Karin G and Eppert, Kolja and Marke, Rene and Isserlin, Ruth and Voisin, Veronique and Bader, Gary D and Zandstra, Peter W and Golub, Todd R and Ebert, Benjamin L and Lu, Jun and Minden, Mark and Wang, Jean C Y and Naldini, Luigi and Dick, John E}},
  issn         = {{1878-3686}},
  language     = {{eng}},
  number       = {{2}},
  pages        = {{214--228}},
  publisher    = {{Cell Press}},
  series       = {{Cancer Cell}},
  title        = {{miR-126 Regulates Distinct Self-Renewal Outcomes in Normal and Malignant Hematopoietic Stem Cells.}},
  url          = {{http://dx.doi.org/10.1016/j.ccell.2015.12.011}},
  doi          = {{10.1016/j.ccell.2015.12.011}},
  volume       = {{29}},
  year         = {{2016}},
}