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| Status |
Public on May 21, 2024 |
| Title |
The S249/T252 site of RB enhanced the function of TRIM24 to activate the mTOR signaling pathway through DUSP2 in prostate cancer [RNA-Seq] |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Prostate cancer (PC) is the most common tumour diagnosis and a serious threat to the lives of men worldwide. It is well recognized that androgens play a unique role in prostate cancer and thus endocrine therapy, represented by androgen deprivation therapy (ADT), is a cornerstone of prostate cancer treatment. However, after ADT treatment, it is inevitable that a number of changes will occur leading from hormone sensitive prostate cancer to castration-resistant prostate cancer (CRPC). RB1 deletion, which is only present in 21% of the population, is the only genomic factor associated with the prognosis of androgen receptor signaling inhibitor therapy. We previously reported that phosphorylated RB has the ability to inhibit p65 in prostate cancer, thereby promoting immune tumour escape and increasing sensitivity to radiotherapy. The N-terminal end of RB also enhances the sensitivity of CDK4/6 inhibitors by recognizing the FXXXV amino acid motif on HDAC5 to down-regulate cell cycle-related genes. Recently, it has been shown that TRIM28 binds to and mediates the ubiquitinated degradation of RB protein. However, the relationship between TRIM24 and RB remains a mystery. In this study, we found that the phosphorylated RB N-terminal can interact with TRIM24 to form a complex that enhances AR signaling. And RB/TRIM24 used DUSP2 as an intermediate bridge to activate the mTOR pathway and promote prostate cancer progression. Finally, we also designed RB-linker-protac, which can attenuate TRIM24 protein levels and inactivate the mTOR signaling pathway, thereby inhibiting prostate cancer. This provides new insights into the treatment of prostate cancer.
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| Overall design |
Comparative gene expression profiling analysis of RNA-seq data for the prostate cancer after knockdown of TRIM24 and RB1 by siRNA, overexpression of RBN and RB(244-255) by plasmids and inhibition of RB1 by RB Protein hydrolysis targeting chimeras (PROTAC) in 22RV1 cells.
Comparative gene expression profiling analysis of RNA-seq data for the C4-2 cells after kncokdown of TRIM24 and RB1
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| Contributor(s) |
Jin X, Liang H |
| Citation(s) |
38514847 |
| Submission date |
Jul 21, 2023 |
| Last update date |
May 22, 2024 |
| Contact name |
Huaiyuan Liang |
| E-mail(s) |
228211116@csu.edu.cn
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| Organization name |
Institute of Urological Cancer, Central South University
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| Street address |
183 Renmin Middle Road
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| City |
Changsha |
| ZIP/Postal code |
410000 |
| Country |
China |
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| Platforms (2) |
| GPL16791 |
Illumina HiSeq 2500 (Homo sapiens) |
| GPL24676 |
Illumina NovaSeq 6000 (Homo sapiens) |
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| Samples (42)
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| GSM7656588 |
22RV1 cells, siTRIM24_1 |
| GSM7656589 |
22RV1 cells, siTRIM24_2 |
| GSM7656590 |
22RV1 cells, siTRIM24_3 |
| GSM7656591 |
22RV1 cells, siRB1_1 |
| GSM7656592 |
22RV1 cells, siRB1_2 |
| GSM7656593 |
22RV1 cells, siRB1_3 |
| GSM7656594 |
22RV1 cells, EV(RBN)_1 |
| GSM7656595 |
22RV1 cells, EV(RBN)_2 |
| GSM7656596 |
22RV1 cells, EV(RBN)_3 |
| GSM7656597 |
22RV1 cells, HA-RBN_1 |
| GSM7656598 |
22RV1 cells, HA-RBN_2 |
| GSM7656599 |
22RV1 cells, HA-RBN_3 |
| GSM7656600 |
22RV1 cells, EV(245-255)_1 |
| GSM7656601 |
22RV1 cells, EV(245-255)_2 |
| GSM7656602 |
22RV1 cells, EV(245-255)_3 |
| GSM7656603 |
22RV1 cells, HA-RB(245-255)_1 |
| GSM7656604 |
22RV1 cells, HA-RB(245-255)_2 |
| GSM7656605 |
22RV1 cells, HA-RB(245-255)_3 |
| GSM7656606 |
22RV1 cells, RBprotac-0 umol/L_1 |
| GSM7656607 |
22RV1 cells, RBprotac-0 umol/L_2 |
| GSM7656608 |
22RV1 cells, RBprotac-0 umol/L_3 |
| GSM7656609 |
22RV1 cells, RBprotac-5 umol/L_1 |
| GSM7656610 |
22RV1 cells, RBprotac-5 umol/L_2 |
| GSM7656611 |
22RV1 cells, RBprotac-5 umol/L_3 |
| GSM7656612 |
22RV1 cells, RBprotac-10 umol/L_1 |
| GSM7656613 |
22RV1 cells, RBprotac-10 umol/L_2 |
| GSM7656614 |
22RV1 cells, RBprotac-10 umol/L_3 |
| GSM8127426 |
C4-2 cells, RBnc-1 |
| GSM8127427 |
C4-2 cells, RBnc-2 |
| GSM8127428 |
C4-2 cells, RBnc-3 |
| GSM8127429 |
C4-2 cells, RBsi-1 |
| GSM8127430 |
C4-2 cells, RBsi-2 |
| GSM8127431 |
C4-2 cells, RBsi-3 |
| GSM8127432 |
C4-2 cells, trim24nc-1 |
| GSM8127433 |
C4-2 cells, trim24nc-2 |
| GSM8127434 |
C4-2 cells, trim24nc-3 |
| GSM8127435 |
C4-2 cells, trim24si-1 |
| GSM8127436 |
C4-2 cells, trim24si-2 |
| GSM8127437 |
C4-2 cells, trim24si-3 |
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| This SubSeries is part of SuperSeries: |
| GSE238211 |
The S249/T252 site of RB enhanced the function of TRIM24 to activate the mTOR signaling pathway through DUSP2 in prostate cancer |
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| Relations |
| BioProject |
PRJNA997255 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE237930_22RV1_cells_EV_RB245-255_gene_fpkm_expression.txt.gz |
535.5 Kb |
(ftp)(http) |
TXT |
| GSE237930_22RV1_cells_EV_RBN_gene_fpkm_expression.txt.gz |
520.8 Kb |
(ftp)(http) |
TXT |
| GSE237930_22RV1_cells_RBprotac_gene_fpkm_expression.txt.gz |
674.3 Kb |
(ftp)(http) |
TXT |
| GSE237930_22RV1_cells_siNC_siTRIM24_siRB1_gene_fpkm_expression.txt.gz |
538.6 Kb |
(ftp)(http) |
TXT |
| GSE237930_C4-2_cells__RB_gene_count_expression.txt.gz |
503.0 Kb |
(ftp)(http) |
TXT |
| GSE237930_C4-2_cells__TRIM24_gene_count_expression.txt.gz |
530.2 Kb |
(ftp)(http) |
TXT |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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