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Series GSE250480 Query DataSets for GSE250480
Status Public on Dec 20, 2023
Title Aberrant upregulation of RUNX3 activates developmental genes to drive metastasis in gastric cancer (HiChIP)
Organism Homo sapiens
Experiment type Other
Summary Gastric cancer metastasis is a major cause of mortality worldwide. Inhibition of RUNX3 in gastric cancer cell lines reduced migration, invasion, and anchorage independent growth in vitro. Following splenic inoculation, CRISPR-mediated RUNX3-knockout HGC-27 cells show suppression of xenograft growth and liver metastasis. We interrogated the potential of RUNX3 as a metastasis driver in gastric cancer by profiling its target genes. Transcriptomic analysis revealed strong involvement of RUNX3 in the regulation of multiple developmental pathways, consistent with the notion that RUNX family genes are master regulators of development. RUNX3 promoted “cell migration” and “extracellular matrix” programs, which are necessary for metastasis. Of note, we found pro-metastatic genes WNT5A, CD44 and VIM among the top differentially expressed genes in RUNX3-knockout versus control cells. Chromatin immunoprecipitation sequencing and HiChIP analyses revealed that RUNX3 bound to the enhancers and promoters of these genes, suggesting that they are under direct transcriptional control by RUNX3. We show that RUNX3 promoted metastasis in part through its upregulation of WNT5A to promote migration, invasion, and anchorage-independent growth in various malignancies. Our study therefore reveals the RUNX3-WNT5A axis as a key targetable mechanism for gastric cancer metastasis.
Overall design Chromatin immunoprecipitation DNA-sequencing (ChIP-seq) for active histone modification H3K27ac, H3K4me3, and H3K4me1 as well as the transcription factor RUNX3 in wildtype or RUNX3 knock-out HGC27 cells
Contributor(s) Suda K, Ito Y, Okabe A, Rahmutulla B, Fukuyo M, Kaneda A
Citation(s) 38240752
Submission date Dec 18, 2023
Last update date Feb 14, 2024
Contact name Masaki Fukuyo
Organization name Chiba University
Department Department of Molecular Oncology
Street address 1-8-1 Inohana, Chuo-ku
City Chiba
ZIP/Postal code 260-8670
Country Japan
Platforms (1)
GPL24676 Illumina NovaSeq 6000 (Homo sapiens)
Samples (1)
GSM7979670 HGC27, wt, H3K27ac HiChIP, rep1
This SubSeries is part of SuperSeries:
GSE250481 Aberrant upregulation of RUNX3 activates developmental genes to drive metastasis in gastric cancer.
BioProject PRJNA1054139

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Supplementary file Size Download File type/resource
GSE250480_RAW.tar 1.7 Gb (http)(custom) TAR (of HIC)
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Raw data are available in SRA

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