ESPADINHA, Anne-Sophie; PROUZET-MAULEON, Valerie; CLAVEROL, Stephane; LAGARDE, Valerie; BONNEU, Marc; MAHON, Francois-Xavier; CARDINAUD, Bruno

doi:10.18632/oncotarget.19192

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ESPADINHA, Anne-Sophie
Biothérapies des maladies génétiques et cancers

PROUZET-MAULEON, Valerie
Biothérapies des maladies génétiques et cancers

CLAVEROL, Stephane
Plateforme Protéome [Bordeaux]

Article de revue

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Oncotarget. 2017-09-29, vol. 8, n° 44, p. 76174-76188

Résumé en anglais

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.< Réduire

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

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