Identification of TRIM24-dependent gene expression programs in prostate cancer cells.
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE69330 | GEO | 2016/05/27
SECONDARY ACCESSION(S): PRJNA285230
REPOSITORIES: GEO
Similar Datasets
Project description:We report a novel and important role for the TRIM24-dependent transcriptional program in promoting prostate cancer progression to a castration-resistant state.
2016-05-27 | GSE69331 | GEO
Project description: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.
2024-05-22 | GSE238209 | GEO
Project description: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.
2024-05-21 | GSE237930 | GEO
Project description:TRIM24 occupancy and TRIM24-dependent gene expression in prostate cancer cells
| PRJNA285228 | ENA
Project description:In this study, proteomic profiling of TRIM24 interactome in conjunction with shRNA screening of TRIM24 top-interactors nominated that TRIM28 is indispensable for TRIM24 protein stability. We showed that TRIM28 stabilizes TRIM24 against SPOP-mediated ubiquitination and degradation. TRIM28 promotes TRIM24 and AR transcription activity, androgen-dependent and -independent PCa growth. In addition, we demonstrated that TRIM28 level in high in advanced PCa, which drives TRIM24/AR transcription activity in a similar manner to SPOP mutation, which implies that TRIM28 potentially dictates the therapeutic outcome of TRIM24-targeted therapy.
2018-10-05 | GSE108145 | GEO
Project description:In this study, proteomic profiling of TRIM24 interactome in conjunction with shRNA screening of TRIM24 top-interactors nominated that TRIM28 is indispensable for TRIM24 protein stability. We showed that TRIM28 stabilizes TRIM24 against SPOP-mediated ubiquitination and degradation. TRIM28 promotes TRIM24 and AR transcription activity, androgen-dependent and -independent PCa growth. In addition, we demonstrated that TRIM28 level in high in advanced PCa, which drives TRIM24/AR transcription activity in a similar manner to SPOP mutation, which implies that TRIM28 potentially dictates the therapeutic outcome of TRIM24-targeted therapy.
2018-10-05 | GSE108144 | GEO
Project description:EZH2 is frequently over-expressed in aggressive and metastatic solid tumors, including castration resistant prostate cancer (CRPC). We sought to determine EZH2-dependent gene expression programmes in prostate cancer progression, and found an intriguing functional switch of EZH2 from a repressor to an activator during CRPC development. We used microarrays to detail the global profiling of gene expression that are differentially regulated upon EZH2 depletion in two different prostate cancer cell lines. The androgen-dependent prostate cancer cell line LNCaP and the LNCaP-derived androgen-independent cell line LNCaP-abl (abl) were used for this study, as their transcription profiles strongly resemble that of clinical androgen-dependent and castration resistant prostate tumors, respectively. EZH2 was silenced by specific siRNAs in both cell lines, and total RNA was extracted and hybridized on Affymetrix microarrays.
2012-11-30 | E-GEOD-39452 | biostudies-arrayexpress
Project description:More effective therapeutic approaches for castration-resistant prostate cancer (CRPC) are urgently needed, thus reinforcing the need to understand how prostate tumors progress to castration resistance. We have established a novel mouse xenograft model of prostate cancer, KUCaP-2, which expresses the wild-type androgen receptor (AR) and which produces the prostate-specific antigen (PSA). In this model, tumors regress soon after castration, but then reproducibly restore their ability to proliferate after 1 to 2 months without AR mutation, mimicking the clinical behavior of CRPC. In the present study, we used this model to identify novel therapeutic targets for CRPC. Evaluating tumor tissues at various stages by gene expression profiling, we discovered that the prostaglandin E receptor EP4 subtype (EP4) was significantly upregulated during progression to castration resistance. Immunohistochemical results of human prostate cancer tissues confirmed that EP4 expression was higher in CRPC compared with hormone-naïve prostate cancer. Ectopic overexpression of EP4 in LNCaP cells (LNCaP-EP4 cells) drove proliferation and PSA production in the absence of androgen supplementation in vitro and in vivo. Androgen-independent proliferation of LNCaP-EP4 cells was suppressed when AR expression was attenuated by RNA interference. Treatment of LNCaP-EP4 cells with a specific EP4 antagonist, ONO-AE3-208, decreased intracellular cyclic AMP levels, suppressed PSA production in vitro, and inhibited castration-resistant growth of LNCaP-EP4 or KUCaP-2 tumors in vivo. Our findings reveal that EP4 overexpression, via AR activation, supports an important mechanism for castration-resistant progression of prostate cancer. Furthermore, they prompt further evaluation of EP4 antagonists as a novel therapeutic modality to treat CRPC. 4 samples in each group: androgen-dependent growth (AD), castration-induced regression nadir (ND), and castration-resistant regrowth (CR) stages
2010-06-08 | E-GEOD-21887 | biostudies-arrayexpress
Project description:To identify molecular singnal alterations between androgen dependent prostate cancer and castration resistant prostate cancer, we performed interspecies comparative microarray analyses using RNAs prepared from uncastrasion and castration tumor from LNCAP Orhotopic xenograft models of prostate cancer. microarray data from uncastrasion and castration tumor revealed that the gene expression profile is most significantly altered in between androgen dependent prostate cancer and castration resistant prostate cancer. Comparative analyses of LNCAP Orhotopic xenograft models of prostate cancer showed that genes involved in androgen dependent and androgen independent tumor were significantly altered.
2013-04-20 | GSE46218 | GEO
Project description:To identify molecular singnal alterations between androgen dependent prostate cancer and castration resistant prostate cancer, we performed interspecies comparative microarray analyses using RNAs prepared from uncastrasion and castration tumor from LNCAP Orhotopic xenograft models of prostate cancer. microarray data from uncastrasion and castration tumor revealed that the gene expression profile is most significantly altered in between androgen dependent prostate cancer and castration resistant prostate cancer. Comparative analyses of LNCAP Orhotopic xenograft models of prostate cancer showed that genes involved in androgen dependent and androgen independent tumor were significantly altered. We prepared RNA samples from 4 samples uncastrasion and 4 samples castration tumors from LNCAP Orhotopic xenograft models of prostate cancer . High-quality RNA samples were subjected to microarray analysis using the Affymetrix Human Gene 2.0 ST platform, and only those results that passed examinations for quality assurance and quality control of the Human Gene 2.0 ST arrays were retrieved. In total, we obtained gene expression profiles from the following samples: 4 samples uncastrasion and 4 samples castration tumors
2013-04-20 | E-GEOD-46218 | biostudies-arrayexpress