Dataset Information


Regulation of STAT3 by histone deacetylase-3 in diffuse large B-cell lymphoma: implications for therapy.

ABSTRACT: Diffuse large B-cell lymphoma (DLBCL) with an activated B-cell (ABC) gene-expression profile has been shown to have a poorer prognosis compared with tumors with a germinal center B-cell type. ABC cell lines have constitutive activation of STAT3; however, the mechanisms regulating STAT3 signaling in lymphoma are unknown. In studies of class-I histone deacetylase (HDAC) expression, we found overexpression of HDAC3 in phospho STAT3-positive DLBCL and the HDAC3 was found to be complexed with STAT3. Inhibition of HDAC activity by panobinostat (LBH589) increased p300-mediated STAT3(Lys685) acetylation with increased nuclear export of STAT3 to the cytoplasm. HDAC inhibition abolished STAT3(Tyr705) phosphorylation with minimal effect on STAT3(Ser727) and JAK2 tyrosine activity. pSTAT3(Tyr705)-positive DLBCLs were more sensitive to HDAC inhibition with LBH589 compared with pSTAT3(Tyr705)-negative DLBCLs. This cytotoxicity was associated with downregulation of the direct STAT3 target Mcl-1. HDAC3 knockdown upregulated STAT3(Lys685) acetylation but prevented STAT3(Tyr705) phosphorylation and inhibited survival of pSTAT3-positive DLBCL cells. These studies provide the rationale for targeting STAT3-positive DLBCL tumors with HDAC inhibitors.

PROVIDER: S-EPMC3625618 | BioStudies |

REPOSITORIES: biostudies

Similar Datasets

| S-EPMC6625855 | BioStudies
| S-EPMC6245852 | BioStudies
| S-EPMC3875539 | BioStudies
| S-EPMC3507146 | BioStudies
2019-05-01 | GSE123398 | GEO
| S-EPMC5907493 | BioStudies
| S-EPMC4184926 | BioStudies
| S-EPMC2275028 | BioStudies
| E-GEOD-43272 | BioStudies
| S-EPMC4165599 | BioStudies