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| Status |
Public on Jun 01, 2021 |
| Title |
AP-2α Regulates S-phase and is a Marker for Sensitivity to PI3K-inhibitor Buparlisib in Colon Cancer [RNA-seq] |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Abstract:AP-2α (encoded by TFAP2A) functions as a tumor suppressor and influences response to therapy in several cancer types. We aimed to characterize regulation of the transcriptome by AP-2α in colon cancer.
Results: Knockout of TFAP2A induced significant alterations in the transcriptome including repression of TGM2, identified as a primary gene target of AP-2α. Loss of AP-2α delayed progression through S-phase into G2/M and decreased phosphorylation of AKT, effects that were mediated through regulation of TGM2. Buparlisib (BKM120) repressed in vitro invasiveness of HCT116 and LS-180; however, loss of AP-2α induced resistance to Buparlisib. Similarly, Buparlisib repressed PHH3 and growth of tumor xenografts and increased overall survival of tumor-bearing mice, whereas, loss of AP-2α induced resistance to the effect of PI3K inhibition.
Conclusion: Loss of AP-2α in colon cancer leads to prolonged S-phase through altered activation of AKT leading to resistance to the PI3K inhibitor, Buparlisib. The findings demonstrate an important role for AP-2α in regulating progression through the cell cycle and indicates that AP-2α is a marker for response to PI3K inhibitors.
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| Overall design |
Experimental Design: CRISPR-Cas9 and shRNA were used to eliminate TFAP2A expression in HCT116 and LS-180 colon cancer cell lines. AP-2a target genes were identified with RNA-seq and ChIP-seq. Effects on cell cycle were characterized in cells synchronized with aphidicolin and analyzed by FACS and Premo FUCCI. Effects on invasion and tumorigenesis were determined by invasion assay, growth of xenografts and phospho-histone H3 (PHH3).
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| Contributor(s) |
Beck AC, Cho E, White JR, Paemka L, Li T, Gu VW, Thompson DT, Koch KE, Wu VT, Landers SR, Pamatmat AJ, Kulak MV, Weigel RJ |
| Citation missing |
Has this study been published? Please login to update or notify GEO. |
| |
| Submission date |
Jul 27, 2020 |
| Last update date |
Jun 01, 2021 |
| Contact name |
Tiandao Li |
| Organization name |
Washington University
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| Street address |
4444 Forest Park Ave
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| City |
St Louis |
| State/province |
MO |
| ZIP/Postal code |
63108 |
| Country |
USA |
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| Platforms (1) |
| GPL16791 |
Illumina HiSeq 2500 (Homo sapiens) |
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| Samples (12)
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| This SubSeries is part of SuperSeries: |
| GSE155169 |
AP-2α Regulates S-phase and is a Marker for Sensitivity to PI3K-inhibitor Buparlisib in Colon Cancer |
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| Relations |
| BioProject |
PRJNA648876 |
| SRA |
SRP273704 |
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