NGDC - GSA for Human

HRA003740

HRA003740.xlsx

Title:

Fimepinostat impairs NFkB and PI3K/AKT signaling and enhances gemcitabine efficacy in H3K27M-mutated diffuse intrinsic pontine glioma

Release date:

2023-12-05

Description:

Diffuse intrinsic pontine gliomas (DIPG) are the most aggressive pediatric brainstem tumors. Currently, there is no cure for DIPG. Here, using drug screening of a set of epigenetic compounds with multiple patient-derived DIPG cells, we demonstrated that gemcitabine and fimepbinostat have anti-tumor efficacy in H3.3K27M DIPG. Firstly, we showed that gemcitabine treatment increased chromatin accessibility of p53 at apoptosis-related genes loci. Notably, the H3.3K27M mutation facilitates gemcitabine-induced apoptosis in DIPG. However, we showed that gemcitabine treatment activates cGAS-STING signaling through induction of long terminal repeat (LTR) elements, which consequently induced RELB-mediated non-canonical NFkb signaling. We showed that RELB is a survival factor in DIPG. Remarkably, through small scale drug screen, we found that fimepbinostat has the synergism with gemcitabine to prevent cell growth, mainly by suppressing RELB-mediated non-canonical NFkb signaling.

Data Accessibility:

Controlled access Request Data

BioProject:

PRJCA014208

Study type:

Disease Study

Disease name:

brain stem glioma

Data Access Committee

For each controlled access study, there is a corresponding Data Access Committee(DAC) to determine the access permissions. Access to actual data files is not managed by NGDC.

DAC NO.:

HDAC000387

DAC name:

Tsinghua DIPG team

Contact person:

Xi Qiaoran

Email:

xiqiaoran@mail.tsinghua.edu.cn

Description:

Xi lab in school of life sciences,Tsinghua University

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