Oncotarget

Research Papers:

A tyrosine kinase-STAT5-miR21-PDCD4 regulatory axis in chronic and acute myeloid leukemia cells

Anne-Sophie Espadinha, Valérie Prouzet-Mauléon, Stéphane Claverol, Valérie Lagarde, Marc Bonneu, François-Xavier Mahon and Bruno Cardinaud _

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Oncotarget. 2017; 8:76174-76188. https://doi.org/10.18632/oncotarget.19192

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Abstract

Anne-Sophie Espadinha1,2, Valérie Prouzet-Mauléon1,2, Stéphane Claverol3, Valérie Lagarde1,2, Marc Bonneu3,4, François-Xavier Mahon1,2 and Bruno Cardinaud1,2,4

1University of Bordeaux, INSERM U1035, Bordeaux, France

2University of Bordeaux, INSERM U1218, Bordeaux, France

3University of Bordeaux, Plateforme Protéome, CGFB, Bordeaux, France

4Bordeaux Institut National Polytechnique, Bordeaux, France

Correspondence to:

Bruno Cardinaud, email: [email protected]

Keywords: CML, STAT5, miR-21, microRNA, leukemia

Received: August 11, 2016     Accepted: June 13, 2017     Published: July 12, 2017

ABSTRACT

MicroRNAs (miRNAs) are regulators of several key patho-physiological processes, including cell cycle and apoptosis. Using microarray-based miRNA profiling in K562 cells, a model of chronic myeloid leukemia (CML), we found that the oncoprotein BCR-ABL1 regulates the expression of miR-21, an “onco-microRNA”, found to be overexpressed in several cancers. This effect relies on the presence of two STAT binding sites on the promoter of miR-21, and on the phosphorylation status of STAT5, a transcription factor activated by the kinase activity of BCR-ABL1. Mir-21 regulates the expression of PDCD4 (programmed cell death protein 4), a tumor suppressor identified through a proteomics approach. The phosphoSTAT5 — miR-21 — PDCD4 pathway was active in CML primary CD34+ cells, but also in acute myeloid leukemia (AML) models like MV4.11 and MOLM13, where the constitutively active tyrosine kinase FLT3-ITD plays a similar role to BCR-ABL1 in the K562 cell line.


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