The role of microRNA-196a and microRNA-196b as ERG regulators in acute myeloid leukemia and acute T-lymphoblastic leukemia.
Overexpression of the ETS transcription factor ERG is an adverse prognostic factor in adult patients with acute myeloid leukemia (AML) and T-cell acute lymphoblastic leukemia (T-ALL). We investigated the regulation of ERG by microRNAs and explored their role in hematopoiesis and leukemia. Transfection of precursor molecules of miR-196a and miR-196b induced ERG downregulation and luciferase assays confirmed binding of miR-196a and miR-196b to the ERG 3'UTR. During in vitro differentiation of CD34(+) cells, miR-196b expression decreased with time, indicating a role for miR-196b in early hematopoiesis. In AML, patients with NPM1-mutations had higher levels of miR-196a and miR-196b compared to NPM1-wildtype. In T-ALL patients, miR-196a and miR-196b expression was associated with an immature immunophenotype, and expression of CD34 and CD33. In conclusion, our results identify miR-196a and miR-196b as ERG regulators and implicate a potential role for these miRNAs in acute leukemia.
Coskun
Ebru
E
Department of Hematology and Oncology, Charité University Hospital Berlin, Campus Benjamin Franklin, Hindenburgdamm 30, Berlin, Germany.
von der Heide
Eva Kristin
EK
Schlee
Cornelia
C
Kühnl
Andrea
A
Gökbuget
Nicola
N
Hoelzer
Dieter
D
Hofmann
Wolf-Karsten
WK
Thiel
Eckhard
E
Baldus
Claudia D
CD
D015973:Gene Expression Regulation, Leukemic / Q000235:genetics*; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000235:genetics*; D035683:MicroRNAs / Q000235:genetics*; D000090243:Nucleophosmin; D054218:Precursor T-Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015534:Trans-Activators / Q000096:biosynthesis / Q000235:genetics*; D000071230:Transcriptional Regulator ERG; D014162:Transfection
C072312:ERG protein, human; C542543:MIRN196 microRNA, human; D035683:MicroRNAs; C000716967:NPM1 protein, human; D015534:Trans-Activators; D000071230:Transcriptional Regulator ERG; D000090243:Nucleophosmin