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cells, mirb, expression, pubmed, mice, scholar, hoxa, google, leukaemia, cas, fas, genes, meis, cell, fig, normal, target, mllrearranged, mirna, human, mllaf, usa, central, aml, significantly, mouse, control, leukaemic, targets, mirbmllaf, samples, secondary, leukemia, leukemogenesis, mll, analysis, acute, primary, myeloid, shown, supplementary, panel, blood, nature, oncogenic, transplantation, recipient, repression, gene, tumoursuppressor,

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nature portfolio permissions reprints contributed reagents/analytic tools privacy policy mscv-pig-mir-196b + mscvneo-mll-af9 mscv-pig-mir-196b+miy-mll-af9 mscv-pig-mir-196b + mscvneo-mll-ell mir-196b+mll-af9-induced leukaemia granulocyte-macrophage colony-stimulating factor pgk-puromycin-ires-gfp cassette advertising mir-196b+mll-af9 donor cells mir-196b+mll-af9 leukaemia cells mir-196b+mll-af9+fas tissue lin−sca1+c-kit+flk2− lin−sca1+c-kit+flk2+ anti-fas antibody-induced apoptosis full access mscv-pig + mscvneo-mll-af9 mll-fusion-mediated cell transformation thermo scientific mscv-pig+miy-mll-af9 mir-196b-mediated gene regulations reverses mir-196b-mediated phenotypes mll-enl-mediated cellular immortalization research scholar grant mscv-pig + mscvneo-mll-ell social media nature 435 nature 466 nature 442 nature mir-196b+mll-af9 tissue mscv-pig-mir-196b + mscvneo mscv-pig-mir-196b+miy prevents mir-196b-mediated repression mir-196b+mll-af9 mice mir-196b+mll-af9 cells mll-fusion-mediated leukemogenesis mir-196b-mediated gene regulation leukaemia stem-cell development kits leukaemia stem/initiating cells intramural research program mll-fusion-mediated leukemogensis translational research grant mll-fusion gene leukemia lin−sca1−c-kit+ haematopoietic stem/progenitor cells herbal medicine research

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• AP-1—The Jun proteins: oncogenes or tumor suppressors in disguise?
• MicroRNAs: a safeguard against turmoil?

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      headline:miR-196b directly targets both HOXA9/MEIS1 oncogenes and FAS tumour suppressor in MLL-rearranged leukaemia
      description:HOXA9 and MEIS1 have essential oncogenic roles in mixed lineage leukaemia (MLL)-rearranged leukaemia. Here we show that they are direct targets of miRNA-196b, a microRNA (miRNA) located adjacent to and co-expressed with HOXA9, in MLL-rearranged leukaemic cells. Forced expression of miR-196b significantly delays MLL-fusion-mediated leukemogenesis in primary bone marrow transplantation through suppressing Hoxa9/Meis1 expression. However, ectopic expression of miR-196b results in more aggressive leukaemic phenotypes and causes much faster leukemogenesis in secondary transplantation than MLL fusion alone, likely through the further repression of Fas expression, a proapoptotic gene downregulated in MLL-rearranged leukaemia. Overexpression of FAS significantly inhibits leukemogenesis and reverses miR-196b-mediated phenotypes. Targeting Hoxa9/Meis1 and Fas by miR-196b is probably also important for normal haematopoiesis. Thus, our results uncover a previously unappreciated miRNA-regulation mechanism by which a single miRNA may target both oncogenes and tumour suppressors, simultaneously, or, sequentially, in tumourigenesis and normal development per cell differentiation, indicating that miRNA regulation is much more complex than previously thought. HOX9AandMEIS1are key oncogenes in MLL-rearranged leukaemia. miRNA-196b is shown here to directly suppress their expression and delay MLL-fusion-mediated leukaemia, but to also cause an aggressive leukaemia phenotype when expressed ectopically, suggesting that it targets tumour suppressors as well.
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