Reduced NCOR2 expression accelerates androgen deprivation therapy failure in prostate cancer

Long, Mark D.; Jacobi, Justine J.; Singh, Prashant; Llimos, Gerard; Wani, Sajad A.; Rowsam, Aryn M.; Rosario, Spencer R.; Hoogstraat, Marlous; Linder, Simon; Kirk, Jason; Affronti, Hayley C.; Bergman, Andries M.; Zwart, Wilbert; Campbell, Moray J.; Smiraglia, Dominic J.

doi:10.1016/j.celrep.2021.110109

Cited by 26 publications

(28 citation statements)

References 96 publications

(137 reference statements)

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“…Immunoprecipitation of sonicated material was performed with antibodies against VDR (D2K6W; Cell Signaling Technology) or IgG (Rabbit IgG sc2729—Santa Cruz Biotechnology) for 16 hours, and antibody/bead complexes isolated with Magna ChIP Protein A+G magnetic beads (Millipore). Complexes were washed, reverse cross-linked, and treated sequentially with RNase and proteinase K prior to DNA isolation, as described previously ( 32 ).…”

Section: Methodsmentioning

confidence: 99%

“…Functional annotation of gene sets: Pathway enrichment analysis and gene set enrichment analysis (GSEA) were performed using gene sets from the Molecular signatures database (MSigDB). For transcript-aware analyses, the FASTQ files were aligned with ( 36 ) and differentially enriched transcripts were identified using ( 37 ) in a similar workflow to , as described previously ( 32 ).…”

Section: Methodsmentioning

confidence: 99%

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African American Prostate Cancer Displays Quantitatively Distinct Vitamin D Receptor Cistrome-transcriptome Relationships Regulated by BAZ1A

Siddappa

Hussain

Wani

et al. 2023

Cancer Research Communications

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African American (AA) prostate cancer associates with vitamin D3 deficiency, but vitamin D receptor (VDR) genomic actions have not been investigated in this context. We undertook VDR proteogenomic analyses in European American (EA) and AA prostate cell lines and four clinical cohorts. Rapid immunoprecipitation mass spectrometry of endogenous protein (RIME) analyses revealed that nonmalignant AA RC43N prostate cells displayed the greatest dynamic protein content in the VDR complex. Likewise, in AA cells, Assay for Transposase-Accessible Chromatin using sequencing established greater 1α,25(OH)2D3-regulated chromatin accessibility, chromatin immunoprecipitation sequencing revealed significant enhancer-enriched VDR cistrome, and RNA sequencing identified the largest 1α,25(OH)2D3-dependent transcriptome. These VDR functions were significantly corrupted in the isogenic AA RC43T prostate cancer cells, and significantly distinct from EA cell models. We identified reduced expression of the chromatin remodeler, BAZ1A, in three AA prostate cancer cohorts as well as RC43T compared with RC43N. Restored BAZ1A expression significantly increased 1α,25(OH)2D3-regulated VDR-dependent gene expression in RC43T, but not HPr1AR or LNCaP cells. The clinical impact of VDR cistrome-transcriptome relationships were tested in three different clinical prostate cancer cohorts. Strikingly, only in AA patients with prostate cancer, the genes bound by VDR and/or associated with 1α,25(OH)2D3-dependent open chromatin (i) predicted progression from high-grade prostatic intraepithelial neoplasia to prostate cancer; (ii) responded to vitamin D3 supplementation in prostate cancer tumors; (iii) differentially responded to 25(OH)D3 serum levels. Finally, partial correlation analyses established that BAZ1A and components of the VDR complex identified by RIME significantly strengthened the correlation between VDR and target genes in AA prostate cancer only. Therefore, VDR transcriptional control is most potent in AA prostate cells and distorted through a BAZ1A-dependent control of VDR function. Significance: Our study identified that genomic ancestry drives the VDR complex composition, genomic distribution, and transcriptional function, and is disrupted by BAZ1A and illustrates a novel driver for AA prostate cancer.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

African American Prostate Cancer Displays Quantitatively Distinct Vitamin D Receptor Cistrome-transcriptome Relationships Regulated by BAZ1A

Siddappa

Hussain

Wani

et al. 2023

Cancer Research Communications

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“…“ RIMS3 ” ( Deng et al, 2022 ) is essential for transmembrane transporter binding activity. “TRAC” ( Long et al, 2021 ) is a protein coding gene related to immunodeficiency. “ FMOD ” ( Silva et al, 2022 ) can affect the rate of fibrils formation as a biomarker of prostate cancer.…”

Section: Discussionmentioning

confidence: 99%

Identification of a polyamine-related signature and six novel prognostic biomarkers in oral squamous cell carcinoma

Tang

Wu²,

Cheng³

et al. 2023

Front. Mol. Biosci.

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Elevated polyamine levels are required for tumor transformation and development; however, expression patterns of polyamines and their diagnostic potential have not been investigated in oral squamous cell carcinoma (OSCC), and its impact on prognosis has yet to be determined. A total of 440 OSCC samples and clinical data were obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO). Consensus clustering was conducted to classify OSCC patients into two subgroups based on the expression of the 17 polyamine regulators. Polyamine-related differentially expressed genes (PARDEGs) among distinct polyamine clusters were determined. To create a prognostic model, PARDEGs were examined in the training cohorts using univariate-Lasso-multivariate Cox regression analyses. Six prognostic genes, namely, “CKS2,” “RIMS3,” “TRAC,” “FMOD,” CALML5,” and “SPINK7,” were identified and applied to develop a predictive model for OSCC. According to the median risk score, the patients were split into high-risk and low-risk groups. The predictive performance of the six gene models was proven by the ROC curve analysis of the training and validation cohorts. Kaplan–Meier curves revealed that the high-risk group had poorer prognosis. Furthermore, the low-risk group was more susceptible to four chemotherapy drugs according to the IC50 of the samples computed by the “pRRophetic” package. The correlation between the risk scores and the proportion of immune cells was calculated. Meanwhile, the tumor mutational burden (TMB) value of the high-risk group was higher. Real-time quantitative polymerase chain reaction was applied to verify the genes constructing the model. The possible connections of the six genes with various immune cell infiltration and therapeutic markers were anticipated. In conclusion, we identified a polyamine-related prognostic signature, and six novel biomarkers in OSCC, which may provide insights to identify new treatment targets for OSCC.

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“…As shown by Long et al, loss of NCOR2 (nuclear receptor corepressor 2) was associated with significantly shorter relapse-free survival in patients undergoing adjuvant androgen deprivation therapy (ADT). Both altered gene transcription and epigenetic changes appear to be responsible for the development of the lethal neuroendocrine subtype of PCa (NEPC) [ 68 ].…”

Section: Tumor Microspheroids/organoids In Urologymentioning

confidence: 99%

3D Tumor Models in Urology

Neuhaus

Rabien

Reinhold

et al. 2023

IJMS

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Three-dimensional tumor models have become established in both basic and clinical research. As multicellular systems consisting of tumor and tumor-associated cells, they can better represent tumor characteristics than monocellular 2D cultures. In this review, we highlight the potential applications of tumor spheroids and organoids in the field of urology. Further, we illustrate the generation and characteristics of standardized organoids as well as membrane-based 3D in vitro models in bladder cancer research. We discuss the technical aspects and review the initial successes of molecular analyses in the three major urologic tumor entities: urinary bladder carcinoma (BCa), prostate carcinoma (PCa), and renal cell carcinoma (RCC).

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Reduced NCOR2 expression accelerates androgen deprivation therapy failure in prostate cancer

Cited by 26 publications

References 96 publications

African American Prostate Cancer Displays Quantitatively Distinct Vitamin D Receptor Cistrome-transcriptome Relationships Regulated by BAZ1A

African American Prostate Cancer Displays Quantitatively Distinct Vitamin D Receptor Cistrome-transcriptome Relationships Regulated by BAZ1A

Identification of a polyamine-related signature and six novel prognostic biomarkers in oral squamous cell carcinoma

3D Tumor Models in Urology

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