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| Status |
Public on Jan 26, 2023 |
| Title |
Pharmacological intervention of PRMT5 links the E2F pathway with tumor associated antigens derived from the non-coding genome |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
E2F activity impacts on an extensive gene network mediated in part by PRMT5-dependent arginine methylation which widens its functional role in gene expression control. We show here that the PRMT5-E2F1 axis has an additional and unexpected level of control through facilitating expression of the non-coding genome where long non-coding (lnc) genes are direct targets for PRMT5 and E2F1. The expression of some lncRNAs results in their translation into small proteins, which then give rise to peptides which populate the MHC class I antigen presentation machinery. Pharmacological inhibition of PRMT5 alters the expression of lncRNA genes and thereby the repertoire lncRNA-derived peptides presented as MHC bound peptides. Delayed tumor growth upon PRMT5 inhibition reflects an influx of lncRNA peptide-specific cytotoxic CD8 T cells. When presented to the immune system as a stand-alone therapeutic vaccine, lncRNA-derived MHC-bound peptides are immunogenic and drive a potent anti-tumor T cell response with a significant delay in tumor growth. Our results show that the PRMT5 through its control of the E2F pathway influences expression of the non-coding genome and derived peptides presented to the immune system, which can subsequently be harnessed to deliver an effective stand-alone cancer vaccine. These results have important implications for deploying pharmacological intervention to manipulate gene expression and antigen presentation to the immune system and deploying new types of cancer vaccine. They also indicate that cell cycle control through the E2F pathway is intimately connected with immune recognition.
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| Overall design |
Examination of expression profile of murine (CT26) colorectal cancer cells treated with DMSO (Control) or PRMT5 inhibitor (T1-44). In the experiment, the impact of PRMT5 inhibition on gene expression profiles was monitored. The experiment had 2 samples (CT26 + DMSO, CT26 + T1-44) and was performed in biological triplicate. CT26 + DMSO samples were used as the reference sample to which all others were compared. An analysis was also performed on RNA extracted from tumor samples (Colon26 cells grown in situ in Balb/c mice, treated with DMSO or T1-44). Again the experiment had two treatment conditions (DMSO and T1-44) and was performed in biological triplicate. Tumor samples treated with DMSO were used as the reference sample to which all others were compared.
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| Contributor(s) |
Barczak W, Carr SM, Liu G, Munro S, Nicastri A, Lee L, Ternette N, Klenerman P, Kanapin A, Samsonova A, La Thangue NB |
| Citation(s) |
36841868 |
| Submission date |
Aug 03, 2021 |
| Last update date |
Apr 27, 2023 |
| Contact name |
Alexander Kanapin |
| E-mail(s) |
a.kanapin@gmail.com
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| Phone |
+78123636939
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| Organization name |
St Petersburg Universoty
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| Department |
Institute for Translational Biomedicine
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| Street address |
7/9 University Emb.
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| City |
St. Petersburg |
| ZIP/Postal code |
199034 |
| Country |
Russia |
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| Platforms (1) |
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| Samples (12)
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| GSM5501731 |
CT26 cell line treated with T1-44, replicate 1 |
| GSM5501732 |
CT26 cell line treated with T1-44, replicate 2 |
| GSM5501733 |
CT26 cell line treated with T1-44, replicate 3 |
| GSM5501734 |
CT26 cell line treated with DMSO, replicate 1 |
| GSM5501735 |
CT26 cell line treated with DMSO, replicate 2 |
| GSM5501736 |
CT26 cell line treated with DMSO, replicate 3 |
| GSM5501737 |
Colon26 tumors from mice treated with T1-44, replicate 1 |
| GSM5501738 |
Colon26 tumors from mice treated with T1-44, replicate 2 |
| GSM5501739 |
Colon26 tumors from mice treated with T1-44, replicate 3 |
| GSM5501740 |
Colon26 tumors from mice treated with DMSO, replicate 1 |
| GSM5501741 |
Colon26 tumors from mice treated with DMSO, replicate 2 |
| GSM5501742 |
Colon26 tumors from mice treated with DMSO, replicate 3 |
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| Relations |
| BioProject |
PRJNA751883 |
| SRA |
SRP331028 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE181401_RAW.tar |
2.6 Mb |
(http)(custom) |
TAR (of TXT) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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