样本编号	SAMC2518840
外部数据库编号	GSA-Human: HRS510125
样品名称	TT150630-H3F3A-KD-1
样本标题	TT150630
样品类型	Human sample
物种名称	Homo sapiens
描述信息	tumor tissue derived cell line
样本属性	*该样本包含更多受控访问信息，请通过GSA-Human系统申请项目HRA003740数据获取。
发布日期	2023-12-05
项目编号	PRJCA014208
提交者	Qiaoran Xi (xiqiaoran@mail.tsinghua.edu.cn)
提交单位	Tsinghua University
提交日期	2023-06-18

样本包含数据信息

资源名称	描述
GSA-Human (1)	-
HRA003740 (Controlled Access)	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.

资源名称

描述

GSA-Human (1)

HRA003740 (Controlled Access)

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.