Myc Induces miRNA-Mediated Apoptosis in Response to HDAC Inhibition in Hematologic Malignancies.

ABSTRACT: Alterations in the expression or function of histone deacetylases (HDAC) contribute to the development and progression of hematologic malignancies. Consequently, the development and implementation of HDAC inhibitors has proven to be therapeutically beneficial, particularly for hematologic malignancies. However, the molecular mechanisms by which HDAC inhibition (HDACi) induces tumor cell death remain unresolved. Here, we investigated the effects of HDACi in Myc-driven B-cell lymphoma and five other hematopoietic malignancies. We determined that Myc-mediated transcriptional repression of the miR-15 and let-7 families in malignant cells was relieved upon HDACi, and Myc was required for their upregulation. The miR-15 and let-7 families then targeted and downregulated the antiapoptotic genes Bc

SUBMITTER: Adams CM 

PROVIDER: S-EPMC4738141 | biostudies-literature | 2016 Feb

REPOSITORIES: biostudies-literature