BET protein inhibitor JQ1 downregulates chromatin accessibility and suppresses metastasis of gastric cancer via inactivating RUNX2/NID1 signaling

Oncogenesis
Siqi ZhouXiaoping Zou

Abstract

Chromatin accessibility is critical for tumor development, whose mechanisms remain unclear. As a crucial regulator for chromatin remodeling, BRD4 promotes tumor progression by regulating multiple genes. As a small-molecule inhibitor of BRD4, JQ1 has potent chemotherapeutic activity against various human cancers. However, whether JQ1 has potential anti-tumor effects and how JQ1 regulates global transcription in gastric cancer (GC) remain largely unknown. In this research, we found BRD4 was highly expressed in GC tissues and was significantly associated with poor prognosis. JQ1 inhibited the proliferation and induced apoptosis of GC cells in vitro. Besides, JQ1 suppressed the migration and invasion of cancer cells by inducing MET. Notably, an assay for transposase-accessible chromatin using sequencing (ATAC-seq) data showed that JQ1 obviously downregulated the chromatin accessibility of GC cells and differentially accessible regions were highly enriched for RUNX2-binding motifs. Combinational analysis of ATAC-seq and RNA-seq data discovered NID1 as the downstream target of JQ1 and JQ1 reduced NID1 expression in GC cells. Chromatin immunoprecipitation, luciferase reporter gene assay, and rescue experiments all confirmed that RUNX2...Continue Reading

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Citations

Dec 22, 2020·Journal of Cellular Physiology·Liang LiXi-Long Zheng
Jan 20, 2021·Signal Transduction and Targeted Therapy·Nian WangRui Kang
Mar 25, 2021·Cancer Management and Research·Weizhu ZhaoLigang Xing
Sep 15, 2021·The Biochemical Journal·Jocelyn F Chen, Qin Yan

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Datasets Mentioned

BETA
GES
GSE29272
GSE79973

Methods Mentioned

BETA
RNA-seq
fluorescence-activated cell sorting
PCR
immunoprecipitation
histone acetylation
xenograft
ChIP
Tandem Repeats profiling
transfection
light microscopy

Software Mentioned

GraphPad Prism
GEPIA ( Gene Expression Profiling Interactive Analysis
SPSS
cBot Cluster Generation System
GENEWIZ

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