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The miR-194-5p/BCLAF1 module is responsible for maturation block, cell fate and treatment susceptibility in AML.

ABSTRACT: miRNAs deregulation contributes to cancer. miR-194-5p is up-regulated by the HDAC inhibitor (HDACi) SAHA, negatively modulating BCL2-associated transcription factor 1 (BCLAF1). We prove that the miR-194-5p/BCLAF1 equilibrium regulates differentiation, survival and self-renewal of normal progenitors and acute myeloid leukemia (AML) blasts. This equilibrium is perturbed in AMLs resulting in highly expressed BCLAF1, suppression of miR194-5p, consequently, locking cells into an immature, potentially ‘immortal’ state. HDACis reverse this scenario relocating BCLAF1 from the nucleus to a peri-membrane ring-like cytoplasmic structure, sensitizing the cells to differentiation or apoptosis. miR-194-5p and BCLAF1 are significantly deregulated in a cohort of 60 primary AMLs and get restored by HDACi. Our findings connect responsiveness to treatment to re-instatement of miR-194-5p/BCLAF1 balance. These findings might be exploited for (epi-based) anti-leukemia therapy.

ORGANISM(S): Homo sapiens

PROVIDER: GSE76426 | GEO | 2017/12/20

SECONDARY ACCESSION(S): PRJNA307259

REPOSITORIES: GEO

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