miR-126 Regulates Distinct Self-Renewal Outcomes in Normal and Malignant Hematopoietic Stem Cells.
(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)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/8829996
- author
- organization
- publishing date
- 2016
- 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}}, }