 |
 |
GEO help: Mouse over screen elements for information. |
|
| Status |
Public on May 09, 2019 |
| Title |
Therapeutic targeting of BRD4 in head neck squamous cell carcinoma |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
|
| Summary |
The bromodomain and extraterminal family members are epigenetic readers and transcriptional coactivators which are critically involved in various biological processes including tumorigenesis. BRD4 has been increasingly appreciated as a key oncogene and promising anticancer target. Here, we sought to characterize the expression of BRD4 and its tumorigenic roles as well as therapeutic targeting in HNSCC. Expression of BRD4 mRNA and protein was determined by bioinformatics interrogation of public available databases, primary HNSCC samples and 4NQO-induced HNSCC animal model. The tumorigenic roles of BRD4 in HNSCC were evaluated by genetic and pharmacological approach in vitro and in vivo. Therapeutic efficiency of BRD4 targeting by JQ1 was assessed in three preclinical models including xenograft model, 4NQO-induced model and patients-derived xenograft model. Gene candidates responsible for therapeutic effects of JQ1 were identified by transcriptional profiling in HNSCC cells after JQ1 exposure. Significant upregulation of BRD4 was found in primary HNSCC samples and 4NQO-induced HNSCC model. Its overexpression associated with aggressive clinicopathological features and inferior overall and disease-free survival. BRD4 depletion by genetic silencing or pharmacological inhibition impaired cell proliferation, migration and invasion and reduced tumor growth and metastasis in vivo. Transcriptional profiling of HNSCC cells following JQ1 exposure identified hundreds of genes which might mediated its antitumor effects and enriched in cancer-relevant pathways. A novel prognostic risk score derived from JQ1-regualted genes was developed to stratify patients into subgroups with favorable or inferior prognosis. Our findings reveal that BRD4 serves as a novel oncogene driving cancer progression and a robust prognostic biomarker in HNSCC. Therapeutic targeting of BRD4 represents a potent and promising strategy against HNSCC.
|
| |
|
| Overall design |
JQ1 induced gene expression in human head neck squamous cell carcinoma cells were detected at 24 hours after exposure to dose of 0, 0.5 μM. Two different kinds of HNSCC cells Cal27 and Fadu were utilized in this study.
|
| |
|
| Contributor(s) |
Wu Y, Wang Y, Diao P, Zhang W, Li J, Ge H, Song Y, Li Z, Wang D, Liu L, Jiang H, Cheng J |
| Citation(s) |
31037138 |
| |
| Submission date |
Nov 14, 2018 |
| Last update date |
May 09, 2019 |
| Contact name |
Jie Cheng |
| E-mail(s) |
jiecheng_njmu@163.com
|
| Phone |
86-25-85031880
|
| Organization name |
Nanjing Medical University
|
| Street address |
136 Hanzhong Road
|
| City |
Nanjing |
| State/province |
Jiangsu |
| ZIP/Postal code |
210029 |
| Country |
China |
| |
|
| Platforms (1) |
| GPL21185 |
Agilent-072363 SurePrint G3 Human GE v3 8x60K Microarray 039494 [Probe Name Version] |
|
| Samples (4)
|
|
| Relations |
| BioProject |
PRJNA505480 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE122522_Normalized_Data.txt.gz |
7.0 Mb |
(ftp)(http) |
TXT |
| GSE122522_RAW.tar |
49.3 Mb |
(http)(custom) |
TAR (of TXT) |
| Processed data included within Sample table |
| Processed data are available on Series record |
|
|
|
|
 |
Less...
More...