Transcriptional activation of the miR-17-92 cluster is involved in the growth-promoting effects of MYB in human Ph-positive leukemia cells.

Transcriptional activation of the miR-17-92 cluster is involved in the growth-promoting effects of MYB in human Ph-positive leukemia cells. Haematologica. 2018 Aug 03;: Authors: Spagnuolo M, Regazzo G, De Dominici M, Sacconi A, Pelosi A, Korita E, Marchesi F, Pisani F, Magenta A, Lulli V, Cordone I, Mengarelli A, Strano S, Blandino G, Rizzo MG, Calabretta B Abstract MicroRNAs, non-coding regulators of gene expression, are likely to function as important downstream effectors of many transcription factors including MYB. Optimal levels of MYB are required for transformation/maintenance of BCR-ABL1-expressing cells. We investigated whether MYB silencing modulates microRNAs expression in Philadelphia-positive leukemia cells and if MYB-regulated microRNAs are important for the MYB addiction of these cells. 35 microRNAs were modulated by MYB silencing in chronic lymphoid and erythro-myeloid blast crisis BV173 and K562 leukemia cells; 15 of these were concordantly modulated in both lines. We focused on the miR-17-92 cluster because of its oncogenic role in tumors and found that: i) it is a direct MYB target; ii) it partially rescued the impaired proliferation and enhanced apoptosis of MYB-silenced BV173 cells. Moreover, we identified FRZB, a Wnt/β-catenin pathway inhibitor, as a novel target of the miR-17-92 cluster. High expression of MYB in blast cells from two Ph-positive leukemia patients correlated positively with the miR-17-92 cluster...
Source: Haematologica - Category: Hematology Authors: Tags: Haematologica Source Type: research