biostudies-literature00560Lechman EREuropean Research CouncilNCI NIH HHSCanadian Institutes of Health Research214-28https://www.ebi.ac.uk/biostudies/studies/S-EPMC4749543biostudies-literatureUnknown29(2)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.Cancer cellmiR-126 Regulates Distinct Self-Renewal Outcomes in Normal and Malignant Hematopoietic Stem Cells.PMC4749543249845R01 CA121941U24 CA194107Dobson SMLechman ERvan Galen PMinden MTakayama NEbert BLNaldini LNilsson BKennedy JAHermans KGZandstra PWCiceri FDick JEGentner BWang JCBader GDKaufmann KBKrivdova GNucera SEppert KTrotman-Grant AElzinga JNg SWMarke RVoisin VLu JMitchell AIsserlin RSchoof EMGolub TR56falsemiR-126 Regulates Distinct Self-Renewal Outcomes in Normal and Malignant Hematopoietic Stem Cells.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.2016-01-01T00:00:00Z2016 Feb2020-10-29T11:23:18Z2019-03-27T02:08:53ZS-EPMC47495432683266210.1016/j.ccell.2015.12.011