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| Status |
Public on Mar 04, 2020 |
| Title |
Therapeutic targeting of splicing in aggressive prostate cancer |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Androgen deprivation therapy (ADT) is the main therapeutic regimen for patients with advanced prostate cancer (PCa). However, most treated patients invariably develop the castration-resistant disease (i.e., CRPC). Mechanisms underlying CRPC development and maintenance remain poorly understood. Recent studies have established splicing dysregulation as a new molecular hallmark of cancer. However, the functional and clinical relevance of such misregulation have not been systematically explored in PCa. Experimentally, we show that splicing modulator, E7107, can significantly inhibits CRPC cell growth both in vitro and in vivo. To determine the mechanistic origins of therapeutic effect of E7107 in vitro, we treated AR+ LNCaP and AR- PC3 cells with DMSO or E7107 at 10nM for 6 h, followed by deep RNA-seq analysis of rRNA-depleted total RNAs isolated from biological triplicates. Furthermore, to evaluate the activity of E7107 against CRPC in vivo, we utilized Enzalutamide-resistant LAPC9-AI (androgen-independent) and PC3 models. RNA-seq experiments we performed on tumors exactly 4 h after the fifth injection of E7107 (5mg/kg/day, 5-days injection considered as 1-dose treatment). Five tumors were included for each group (vehicle or E7107) for deep RNA-seq.
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| Overall design |
Quantification of changes in RNA splicing and expression in prostate cancer cells and xenograft tumors treated with E7107 to manipulate endogenous spliceosome activity.
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| Contributor(s) |
Zhang D, Hu Q, Tang DG |
| Citation(s) |
32350277 |
| Submission date |
Mar 19, 2019 |
| Last update date |
May 12, 2020 |
| Contact name |
Dingxiao Zhang |
| E-mail(s) |
zdx1980@hnu.edu.cn
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| Phone |
+86-15391542415
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| Organization name |
Hunan University
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| Department |
School of BioMedical Sciences
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| Lab |
Zhang lab
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| Street address |
Yuelushan
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| City |
Changsha |
| State/province |
Hunan |
| ZIP/Postal code |
410082 |
| Country |
China |
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| Platforms (1) |
| GPL24676 |
Illumina NovaSeq 6000 (Homo sapiens) |
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| Samples (32)
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| Relations |
| BioProject |
PRJNA527978 |
| SRA |
SRP188817 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE128515_E7107-PCa_ncounts.csv.gz |
6.1 Mb |
(ftp)(http) |
CSV |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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