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| Status |
Public on Sep 19, 2022 |
| Title |
Targeting CDK12-mediated transcription regulation in anaplastic thyroid carcinoma [RNA-seq] |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Anaplastic thyroid carcinoma (ATC) is the most aggressive type of thyroid cancer, with no effective treatment available. Identification of new anti-ATC drugs represents an urgent need. In this study, we find that ATC cells are highly sensitive to THZ531, a potent inhibitor of the transcriptional cyclin-dependent kinase (CDK), CDK12. Cell-based assays demonstrate that CDK12 inhibition significantly impedes cell cycle progression, induces apoptotic cell death, and impairs colony formation in ATC cells. THZ531 causes a loss of elongating RNA polymerase II and suppresses gene expression in ATC cells. An integrative analysis of gene expression profiles and super-enhancer landscape, combining with functional assays, leads to the discovery of two new ATC cancer genes, ZC3H4 and NEMP1. Furthermore, CDK12 inhibition enhances the sensitivity of ATC cells to doxorubicin-mediated chemotherapy. Thus, these findings indicate that CDK12 is a potential therapeutic target for ATC treatment and its inhibition may help to overcome the chemoresistance in patients with ATC
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| Overall design |
mRNA profiles of CAL-62 treated with DMSO or THZ531 for 6 h were generated by deep sequencing, in duplicate, using Illumina NovaSeq.
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| Contributor(s) |
Geng M, Cao X, Zhang L |
| Citation missing |
Has this study been published? Please login to update or notify GEO. |
| |
| Submission date |
Sep 19, 2019 |
| Last update date |
Sep 20, 2022 |
| Contact name |
Meijuan Geng |
| E-mail(s) |
gengmeijuan@tmu.edu.cn
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| Organization name |
Tianjin Medical Universuty
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| Street address |
No.22 Qixiangtai Road
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| City |
Tianjin |
| ZIP/Postal code |
300070 |
| Country |
China |
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| Platforms (1) |
| GPL24676 |
Illumina NovaSeq 6000 (Homo sapiens) |
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| Samples (6)
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| This SubSeries is part of SuperSeries: |
| GSE137698 |
Targeting CDK12-mediated transcription regulation in anaplastic thyroid carcinoma |
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| Relations |
| BioProject |
PRJNA566341 |
| SRA |
SRP222490 |
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