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| Status |
Public on May 31, 2022 |
| Title |
RNA Polymerase I activity prevents terminal differentiation and growth arrest in colorectal cancer and induce vulnerability for senolytics |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Loss of the tumor suppressor APC, which constitutes the initiating event in the adenoma carcinoma sequence for colorectal cancer (CRC), induces expression of RNA polymerase I (RNAPOL1) transcription machinery and subsequently upregulates rDNA transcription. Targeting RNAPOL1 with a specific inhibitor, CX5461, disrupts nucleolar integrity and induces a disbalance of ribosomal proteins. CX5461-induced growth arrest is irreversible, and exhibits features of senescence as well as terminal differentiation. Mechanistically, CX5461 promotes differentiation in a MIZ1- and Rb-dependent manner. In addition, inhibition of RNAPOL1 renders CRC cells vulnerable towards senolytic agents.
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| Overall design |
RNA-seq of LS174T cells treated with CX5461
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| Contributor(s) |
Wiegering A, Otto C, Kastner C, Schmidt S, Uttinger K, Baluapuri A, Denk S, Rosenfeldt TM, Rosenwald A, Röhrig F, Ade CP, Schülein-Völk C, Diefenbacher M, Germer C, Wolf E, Eilers M |
| Citation(s) |
35673898 |
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| Submission date |
May 24, 2022 |
| Last update date |
Jun 16, 2022 |
| Contact name |
Martin Eilers |
| Organization name |
University of Wuerzburg
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| Department |
Chair for Biochemistry and Molecular Biology
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| Lab |
Martin Eilers
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| Street address |
Am Hubland
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| City |
Wuerzburg |
| ZIP/Postal code |
97074 |
| Country |
Germany |
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| Platforms (1) |
| GPL18573 |
Illumina NextSeq 500 (Homo sapiens) |
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| Samples (12)
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| Relations |
| BioProject |
PRJNA842078 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE204749_RNAseq_edgeR_logFC_table_all_conditions.txt.gz |
899.1 Kb |
(ftp)(http) |
TXT |
| GSE204749_RNAseq_rawcount_matrix_all_conditions.txt.gz |
734.0 Kb |
(ftp)(http) |
TXT |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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