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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Mar 31, 2024 |
| Title |
Transcriptomic analysis of the in vivo effects of CDK8/19 inactivation in 22Rv1 xenografts growing in intact and castrated NSG mice |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
RNA-Seq analysis was carried out to investigate the effects of CDK8/19 inactivation in the tumors formed in intact and castrated NSG mice by different 22Rv1 derivatives, with or without SNX631 treatment. The 22Rv1 derivatives were generated as following: Parental 22Rv1 (Rv1-WT) were transduced with a lentivirus expressing luciferase, yielding the derivative Rv1-Luc. 22Rv1 cells with a double knockout of CDK8 and CDK19 (Rv1-dKO) were made via CRISPR/Cas9. Rv1-dKO cells were further transduced with lentiviruses to generate Rv1-dKO re-expression derivatives that express wild-type CDK19 (Rv1-dKO-CDK19) and the kinase-inactive D173A mutant (Rv1-dKO-CDK19M). SNX631 is a selective and orally bioavalable CDK8/19 inhibtor.
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| Overall design |
Rv1-WT, Rv1-Luc, Rv1-dKO-19 and Rv1-dKO-19M cells were inoculated s.c. (2x10^6 cells in 0.1 mL 50% Matrigel per animal) in the right flank of intact or castrated male NSG mice (8-10 weeks old). Castration was performed by either surgical orchiectomy (for Rv1-WT study) or Degarelix treatment (administered s.c. at 10 mg/kg monthly, for Rv1-Luc, Rv1-dKO-19, Rv1-dKO-19M studies), and tumor inoculation was done 10-14 days post castration. For SNX631 treatment studies, animals were randomly allocated to two study groups when the mean tumor size reached 100-200 mm^3. For Rv1-WT study, the treatment group received SNX631-medicated diet (500 ppm, producing 30-60 mg/kg/day dosage on average) and the control group received the control diet. For Rv1-Luc study, the animals in the control group were dosed with vehicle (70% PEG-400/30% Propylene Glycol, 5 mL/kg, p.o., b.i.d.) and the treatment group was dosed with SNX631 (6 mg/mL solution in the vehicle, 5 mL/kg, p.o., b.i.d.) at 60 mg/kg/day. At the end of studies, tumor xenografts were dissected from euthanized animals using sterilized surgical tools. Pieces of non-necrotic tumor tissues 50~100mm^3 were excised at the margin near midline section for RNA extraction. At least four biological replicates (xenograft tumors from different animals) per study group were analyzed.
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| Contributor(s) |
Li J, Ji H, Roninson IB, Chen M |
| Citation(s) |
38546787 |
| Submission date |
Aug 08, 2023 |
| Last update date |
May 01, 2024 |
| Contact name |
HAO JI |
| E-mail(s) |
ji5@email.sc.edu
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| Phone |
8037774689
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| Organization name |
University of South Carolina
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| Department |
College of Pharmacy
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| Street address |
715 SUMTER ST CLS RM 109
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| City |
COLUMBIA |
| State/province |
SC |
| ZIP/Postal code |
29208 |
| Country |
USA |
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| Platforms (2) |
| GPL20301 |
Illumina HiSeq 4000 (Homo sapiens) |
| GPL24676 |
Illumina NovaSeq 6000 (Homo sapiens) |
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| Samples (66)
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| Relations |
| BioProject |
PRJNA1003454 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE240370_Rv1_invivo_Counts_h.txt.gz |
3.6 Mb |
(ftp)(http) |
TXT |
| GSE240370_Rv1_invivo_Counts_m.txt.gz |
2.0 Mb |
(ftp)(http) |
TXT |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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