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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Apr 22, 2024 |
| Title |
Integrated Enhancer Regulatory Network by Enhancer-Promoter Looping in Gastric Cancer (RNA-seq) |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Enhancer as a cis-regulatory element (CRE), plays a critical role in gene regulation at many stages of cell growth. Meanwhile, enhancers in cancer cells also act as a regulator controlling oncogene transcription. In this study, we did a comprehensive analysis of long-range chromatin interactions, histone modifications, chromatin status, and expressions of two gastric cancer (GC) cell lines, compared with a human normal epithelial cell line. We found that GC-specific enhancers marked by histone modifications in gastric cancer can activate a population of genes including some oncogenes by enhancer-promoter (E-P) interactions. In addition, motif analysis of E-P interacted enhancers showed that three GC-specific TF sequences may regulate enhancer-interacting gene activation. We found MYB which is crucial for GC cellular growth and is activated by TCF7 regulated E-P loop. To validate this mechanism, we applied CRISPRi (dCas9-KRAB) induced transcriptional regulatory element inactivation in our target enhancer, the growth assay resulted in significant inhibition of cell growth in two GC cell lines. In conclusion, we found oncogene activation by aberrant loop formation that contributes to tumorigenesis in GC.
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| Overall design |
To investigate the function of MYB and TCF7 in gastric cancer cells, we obtained MYB and TCF7 knockdown SNU719 and YCC10 gastric cancer cell lines by siRNA and CRISPRi
We then performed gene expression profiling analysis using data obtained from RNA-seq of before and after MYB or TCF7 knockdown in two cell lines (SNU719_siCtrl, SNU719_siMYB, YCC10_siCtrl, YCC10_siMYB; SNU719_siCtrl, SNU719_siTCF7, YCC10_siCtrl, YCC10_siTCF7; SNU719_CRISPRi_sgCtrl, SNU719_CRISPRi_sgMYB-E3, YCC10_CRISPRi_sgCtrl, YCC10_CRISPRi_sgMYB-E3).
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| Contributor(s) |
Zhu T, Okabe A, Fukuyo M, Kaneda A |
| Citation(s) |
38720882 |
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| Submission date |
Nov 12, 2023 |
| Last update date |
Jul 24, 2024 |
| Contact name |
Masaki Fukuyo |
| E-mail(s) |
fukuyo@chiba-u.jp
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| Organization name |
Chiba University
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| Department |
Department of Molecular Oncology
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| Street address |
1-8-1 Inohana, Chuo-ku
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| City |
Chiba |
| ZIP/Postal code |
260-8670 |
| Country |
Japan |
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| Platforms (2) |
| GPL18573 |
Illumina NextSeq 500 (Homo sapiens) |
| GPL24676 |
Illumina NovaSeq 6000 (Homo sapiens) |
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| Samples (16)
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| GSM7892634 |
SNU719, MYB, KD, siCtrl, rep 1 |
| GSM7892635 |
SNU719, MYB, KD, siCtrl, rep 2 |
| GSM7892636 |
YCC10, MYB, KD, siCtrl, rep 1 |
| GSM7892637 |
YCC10, MYB, KD, siCtrl, rep 2 |
| GSM7892638 |
SNU719, MYB, KD, siMYB, rep 1 |
| GSM7892639 |
SNU719, MYB, KD, siMYB, rep 2 |
| GSM7892640 |
YCC10, MYB, KD, siMYB, rep 1 |
| GSM7892641 |
YCC10, MYB, KD, siMYB, rep 2 |
| GSM7892642 |
SNU719, TCF7, KD, siCtrl, rep 1 |
| GSM7892643 |
YCC10, TCF7, KD, siCtrl, rep 1 |
| GSM7892644 |
SNU719, TCF7, KD, siTCF7, rep 1 |
| GSM7892645 |
YCC10, TCF7, KD, siTCF7, rep 1 |
| GSM7892646 |
SNU719, CRISPRi, sgCtrl, rep 1 |
| GSM7892647 |
YCC10, CRISPRi, sgCtrl, rep 1 |
| GSM7892648 |
SNU719, CRISPRi, sgMYB-E3, rep 1 |
| GSM7892649 |
YCC10, CRISPRi, sgMYB-E3, rep 1 |
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| This SubSeries is part of SuperSeries: |
| GSE247539 |
Integrated Enhancer Regulatory Network by Enhancer-Promoter Looping in Gastric Cancer |
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| Relations |
| BioProject |
PRJNA1039487 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE247538_genes.fpkm_tracking.txt.gz |
1.3 Mb |
(ftp)(http) |
TXT |
SRA Run Selector |
| Raw data are available in SRA |
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