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Series GSE128515 Query DataSets for GSE128515
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
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.
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.
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
Phone +86-15391542415
Organization name Hunan University
Department School of BioMedical Sciences
Lab Zhang lab
Street address Yuelushan
City Changsha
State/province Hunan
ZIP/Postal code 410082
Country China
Platforms (1)
GPL24676 Illumina NovaSeq 6000 (Homo sapiens)
Samples (32)
GSM3678270 LNCAP-DMSO-6h-rep1
GSM3678271 LNCAP-DMSO-6h-rep2
GSM3678272 LNCAP-DMSO-6h-rep3
BioProject PRJNA527978
SRA SRP188817

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Supplementary file Size Download File type/resource
GSE128515_E7107-PCa_ncounts.csv.gz 6.1 Mb (ftp)(http) CSV
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Raw data are available in SRA
Processed data are available on Series record

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