7 results on '"Petricca J"'
Search Results
2. CRISPRi screens reveal a DNA methylation-mediated 3D genome dependent causal mechanism in prostate cancer
- Author
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Ahmed, M. (Musaddeque), Soares, F. (Fraser), Xia, J.-H. (Ji-Han), Yang, Y. (Yue), Li, J. (Jing), Guo, H. (Haiyang), Su, P. (Peiran), Tian, Y. (Yijun), Lee, H. J. (Hyung Joo), Wang, M. (Miranda), Akhtar, N. (Nayeema), Houlahan, K. E. (Kathleen E.), Bosch, A. (Almudena), Zhou, S. (Stanley), Mazrooei, P. (Parisa), Hua, J. T. (Junjie T.), Chen, S. (Sujun), Petricca, J. (Jessica), Zeng, Y. (Yong), Davies, A. (Alastair), Fraser, M. (Michael), Quigley, D. A. (David A.), Feng, F. Y. (Felix Y.), Boutros, P. C. (Paul C.), Lupien, M. (Mathieu), Zoubeidi, A. (Amina), Wang, L. (Liang), Walsh, M. J. (Martin J.), Wang, T. (Ting), Ren, S. (Shancheng), Wei, G.-H. (Gong-Hong), He, H. H. (Housheng Hansen), Ahmed, M. (Musaddeque), Soares, F. (Fraser), Xia, J.-H. (Ji-Han), Yang, Y. (Yue), Li, J. (Jing), Guo, H. (Haiyang), Su, P. (Peiran), Tian, Y. (Yijun), Lee, H. J. (Hyung Joo), Wang, M. (Miranda), Akhtar, N. (Nayeema), Houlahan, K. E. (Kathleen E.), Bosch, A. (Almudena), Zhou, S. (Stanley), Mazrooei, P. (Parisa), Hua, J. T. (Junjie T.), Chen, S. (Sujun), Petricca, J. (Jessica), Zeng, Y. (Yong), Davies, A. (Alastair), Fraser, M. (Michael), Quigley, D. A. (David A.), Feng, F. Y. (Felix Y.), Boutros, P. C. (Paul C.), Lupien, M. (Mathieu), Zoubeidi, A. (Amina), Wang, L. (Liang), Walsh, M. J. (Martin J.), Wang, T. (Ting), Ren, S. (Shancheng), Wei, G.-H. (Gong-Hong), and He, H. H. (Housheng Hansen)
- Abstract
Prostate cancer (PCa) risk-associated SNPs are enriched in noncoding cis-regulatory elements (rCREs), yet their modi operandi and clinical impact remain elusive. Here, we perform CRISPRi screens of 260 rCREs in PCa cell lines. We find that rCREs harboring high risk SNPs are more essential for cell proliferation and H3K27ac occupancy is a strong indicator of essentiality. We also show that cell-line-specific essential rCREs are enriched in the 8q24.21 region, with the rs11986220-containing rCRE regulating MYC and PVT1 expression, cell proliferation and tumorigenesis in a cell-line-specific manner, depending on DNA methylation-orchestrated occupancy of a CTCF binding site in between this rCRE and the MYC promoter. We demonstrate that CTCF deposition at this site as measured by DNA methylation level is highly variable in prostate specimens, and observe the MYC eQTL in the 8q24.21 locus in individuals with low CTCF binding. Together our findings highlight a causal mechanism synergistically driven by a risk SNP and DNA methylation-mediated 3D genome architecture, advocating for the integration of genetics and epigenetics in assessing risks conferred by genetic predispositions.
- Published
- 2021
3. SETD7 functions as a transcription repressor in prostate cancer via methylating FOXA1.
- Author
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Wang Z, Petricca J, Liu M, Zhang S, Chen S, Li M, Besschetnova A, Patalano S, Venkataramani K, Siegfried KR, Macoska JA, Han D, Gao S, Vedadi M, Arrowsmith CH, He HH, and Cai C
- Subjects
- Male, Humans, Lysine metabolism, Receptors, Androgen genetics, Receptors, Androgen metabolism, Methyltransferases metabolism, Histone Demethylases metabolism, Cell Line, Tumor, Gene Expression Regulation, Neoplastic, Histone-Lysine N-Methyltransferase genetics, Histone-Lysine N-Methyltransferase metabolism, Hepatocyte Nuclear Factor 3-alpha genetics, Hepatocyte Nuclear Factor 3-alpha metabolism, Histones metabolism, Prostatic Neoplasms, Castration-Resistant genetics
- Abstract
Dysregulation of histone lysine methyltransferases and demethylases is one of the major mechanisms driving the epigenetic reprogramming of transcriptional networks in castration-resistant prostate cancer (CRPC). In addition to their canonical histone targets, some of these factors can modify critical transcription factors, further impacting oncogenic transcription programs. Our recent report demonstrated that LSD1 can demethylate the lysine 270 of FOXA1 in prostate cancer (PCa) cells, leading to the stabilization of FOXA1 chromatin binding. This process enhances the activities of the androgen receptor and other transcription factors that rely on FOXA1 as a pioneer factor. However, the identity of the methyltransferase responsible for FOXA1 methylation and negative regulation of the FOXA1-LSD1 oncogenic axis remains unknown. SETD7 was initially identified as a transcriptional activator through its methylation of histone 3 lysine 4, but its function as a methyltransferase on nonhistone substrates remains poorly understood, particularly in the context of PCa progression. In this study, we reveal that SETD7 primarily acts as a transcriptional repressor in CRPC cells by functioning as the major methyltransferase targeting FOXA1-K270. This methylation disrupts FOXA1-mediated transcription. Consistent with its molecular function, we found that SETD7 confers tumor suppressor activity in PCa cells. Moreover, loss of SETD7 expression is significantly associated with PCa progression and tumor aggressiveness. Overall, our study provides mechanistic insights into the tumor-suppressive and transcriptional repression activities of SETD7 in mediating PCa progression and therapy resistance.
- Published
- 2023
- Full Text
- View/download PDF
4. The 5-Hydroxymethylcytosine Landscape of Prostate Cancer.
- Author
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Sjöström M, Zhao SG, Levy S, Zhang M, Ning Y, Shrestha R, Lundberg A, Herberts C, Foye A, Aggarwal R, Hua JT, Li H, Bergamaschi A, Maurice-Dror C, Maheshwari A, Chen S, Ng SWS, Ye W, Petricca J, Fraser M, Chesner L, Perry MD, Moreno-Rodriguez T, Chen WS, Alumkal JJ, Chou J, Morgans AK, Beer TM, Thomas GV, Gleave M, Lloyd P, Phillips T, McCarthy E, Haffner MC, Zoubeidi A, Annala M, Reiter RE, Rettig MB, Witte ON, Fong L, Bose R, Huang FW, Luo J, Bjartell A, Lang JM, Mahajan NP, Lara PN, Evans CP, Tran PT, Posadas EM, He C, Cui XL, Huang J, Zwart W, Gilbert LA, Maher CA, Boutros PC, Chi KN, Ashworth A, Small EJ, He HH, Wyatt AW, Quigley DA, and Feng FY
- Subjects
- Male, Humans, Prostate, Biopsy, 5-Methylcytosine, Prostatic Neoplasms
- Abstract
Analysis of DNA methylation is a valuable tool to understand disease progression and is increasingly being used to create diagnostic and prognostic clinical biomarkers. While conversion of cytosine to 5-methylcytosine (5mC) commonly results in transcriptional repression, further conversion to 5-hydroxymethylcytosine (5hmC) is associated with transcriptional activation. Here we perform the first study integrating whole-genome 5hmC with DNA, 5mC, and transcriptome sequencing in clinical samples of benign, localized, and advanced prostate cancer. 5hmC is shown to mark activation of cancer drivers and downstream targets. Furthermore, 5hmC sequencing revealed profoundly altered cell states throughout the disease course, characterized by increased proliferation, oncogenic signaling, dedifferentiation, and lineage plasticity to neuroendocrine and gastrointestinal lineages. Finally, 5hmC sequencing of cell-free DNA from patients with metastatic disease proved useful as a prognostic biomarker able to identify an aggressive subtype of prostate cancer using the genes TOP2A and EZH2, previously only detectable by transcriptomic analysis of solid tumor biopsies. Overall, these findings reveal that 5hmC marks epigenomic activation in prostate cancer and identify hallmarks of prostate cancer progression with potential as biomarkers of aggressive disease., Significance: In prostate cancer, 5-hydroxymethylcytosine delineates oncogene activation and stage-specific cell states and can be analyzed in liquid biopsies to detect cancer phenotypes. See related article by Wu and Attard, p. 3880., (©2022 The Authors; Published by the American Association for Cancer Research.)
- Published
- 2022
- Full Text
- View/download PDF
5. The cell-free DNA methylome captures distinctions between localized and metastatic prostate tumors.
- Author
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Chen S, Petricca J, Ye W, Guan J, Zeng Y, Cheng N, Gong L, Shen SY, Hua JT, Crumbaker M, Fraser M, Liu S, Bratman SV, van der Kwast T, Pugh T, Joshua AM, De Carvalho DD, Chi KN, Awadalla P, Ji G, Feng F, Wyatt AW, and He HH
- Subjects
- Male, Humans, Epigenome, Prostate pathology, DNA Methylation genetics, Cell-Free Nucleic Acids genetics, Prostatic Neoplasms pathology
- Abstract
Metastatic prostate cancer remains a major clinical challenge and metastatic lesions are highly heterogeneous and difficult to biopsy. Liquid biopsy provides opportunities to gain insights into the underlying biology. Here, using the highly sensitive enrichment-based sequencing technology, we provide analysis of 60 and 175 plasma DNA methylomes from patients with localized and metastatic prostate cancer, respectively. We show that the cell-free DNA methylome can capture variations beyond the tumor. A global hypermethylation in metastatic samples is observed, coupled with hypomethylation in the pericentromeric regions. Hypermethylation at the promoter of a glucocorticoid receptor gene NR3C1 is associated with a decreased immune signature. The cell-free DNA methylome is reflective of clinical outcomes and can distinguish different disease types with 0.989 prediction accuracy. Finally, we show the ability of predicting copy number alterations from the data, providing opportunities for joint genetic and epigenetic analysis on limited biological samples., (© 2022. The Author(s).)
- Published
- 2022
- Full Text
- View/download PDF
6. CRISPRi screens reveal a DNA methylation-mediated 3D genome dependent causal mechanism in prostate cancer.
- Author
-
Ahmed M, Soares F, Xia JH, Yang Y, Li J, Guo H, Su P, Tian Y, Lee HJ, Wang M, Akhtar N, Houlahan KE, Bosch A, Zhou S, Mazrooei P, Hua JT, Chen S, Petricca J, Zeng Y, Davies A, Fraser M, Quigley DA, Feng FY, Boutros PC, Lupien M, Zoubeidi A, Wang L, Walsh MJ, Wang T, Ren S, Wei GH, and He HH
- Subjects
- Animals, CCCTC-Binding Factor genetics, CCCTC-Binding Factor metabolism, Carcinogenesis genetics, Cell Line, Tumor, Humans, Male, Mice, Inbred NOD, Mice, SCID, Polymorphism, Single Nucleotide, Promoter Regions, Genetic genetics, Proto-Oncogene Proteins c-myc genetics, Quantitative Trait Loci genetics, Regulatory Elements, Transcriptional genetics, Risk Factors, Mice, CRISPR-Cas Systems, DNA Methylation, Gene Editing methods, Genetic Predisposition to Disease genetics, Genome-Wide Association Study methods, Prostatic Neoplasms genetics
- Abstract
Prostate cancer (PCa) risk-associated SNPs are enriched in noncoding cis-regulatory elements (rCREs), yet their modi operandi and clinical impact remain elusive. Here, we perform CRISPRi screens of 260 rCREs in PCa cell lines. We find that rCREs harboring high risk SNPs are more essential for cell proliferation and H3K27ac occupancy is a strong indicator of essentiality. We also show that cell-line-specific essential rCREs are enriched in the 8q24.21 region, with the rs11986220-containing rCRE regulating MYC and PVT1 expression, cell proliferation and tumorigenesis in a cell-line-specific manner, depending on DNA methylation-orchestrated occupancy of a CTCF binding site in between this rCRE and the MYC promoter. We demonstrate that CTCF deposition at this site as measured by DNA methylation level is highly variable in prostate specimens, and observe the MYC eQTL in the 8q24.21 locus in individuals with low CTCF binding. Together our findings highlight a causal mechanism synergistically driven by a risk SNP and DNA methylation-mediated 3D genome architecture, advocating for the integration of genetics and epigenetics in assessing risks conferred by genetic predispositions.
- Published
- 2021
- Full Text
- View/download PDF
7. Widespread and Functional RNA Circularization in Localized Prostate Cancer.
- Author
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Chen S, Huang V, Xu X, Livingstone J, Soares F, Jeon J, Zeng Y, Hua JT, Petricca J, Guo H, Wang M, Yousif F, Zhang Y, Donmez N, Ahmed M, Volik S, Lapuk A, Chua MLK, Heisler LE, Foucal A, Fox NS, Fraser M, Bhandari V, Shiah YJ, Guan J, Li J, Orain M, Picard V, Hovington H, Bergeron A, Lacombe L, Fradet Y, Têtu B, Liu S, Feng F, Wu X, Shao YW, Komor MA, Sahinalp C, Collins C, Hoogstrate Y, de Jong M, Fijneman RJA, Fei T, Jenster G, van der Kwast T, Bristow RG, Boutros PC, and He HH
- Subjects
- Gene Expression Profiling methods, Genetic Profile, HEK293 Cells, Humans, Male, MicroRNAs metabolism, Prostate metabolism, RNA Splicing genetics, RNA, Circular, RNA, Untranslated genetics, Sequence Analysis, RNA methods, Transcriptome, Prostatic Neoplasms genetics, RNA genetics, RNA metabolism
- Abstract
The cancer transcriptome is remarkably complex, including low-abundance transcripts, many not polyadenylated. To fully characterize the transcriptome of localized prostate cancer, we performed ultra-deep total RNA-seq on 144 tumors with rich clinical annotation. This revealed a linear transcriptomic subtype associated with the aggressive intraductal carcinoma sub-histology and a fusion profile that differentiates localized from metastatic disease. Analysis of back-splicing events showed widespread RNA circularization, with the average tumor expressing 7,232 circular RNAs (circRNAs). The degree of circRNA production was correlated to disease progression in multiple patient cohorts. Loss-of-function screening identified 11.3% of highly abundant circRNAs as essential for cell proliferation; for ∼90% of these, their parental linear transcripts were not essential. Individual circRNAs can have distinct functions, with circCSNK1G3 promoting cell growth by interacting with miR-181. These data advocate for adoption of ultra-deep RNA-seq without poly-A selection to interrogate both linear and circular transcriptomes., (Copyright © 2019 Elsevier Inc. All rights reserved.)
- Published
- 2019
- Full Text
- View/download PDF
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