Newswire (Published: Tuesday, November 17, 2020, Received: Tuesday, November 17, 2020, 3:52:41 PM CST)

Word Count: 659

2020 NOV 17 (NewsRx) -- By a News Reporter-Staff News Editor at Genomics & Genetics Daily -- Investigators publish new report on Oncology - Prostate Cancer. According to news reporting originating in Dallas, Texas, by NewsRx journalists, research stated, “Transcriptional dysregulation is a hallmark of prostate cancer (PCa). We mapped the RNA polymerase II-associated (RNA Pal II-associated) chromatin interactions in normal prostate cells and PCa cells.”

Funders for this research include NIH Pathway to Independence (PI) Award, National Cancer Institute (NCI), NIH grant, Cancer Prevention and Research Institute of Texas (CPRIT) Individual Investigator Research Award, US Department of Defense Prostate Cancer Research Program (PCRP) Impact Award, Kidney Cancer Specialized Programs of Research Excellence (SPORE) Career Enhancement Program (CEP) award, UT Southwestern startup funds, University of Texas at Dallas (UTD) startup fund, Cecil H. and Ida Green Endowment, CPRIT, National Natural Science Foundation of China (NSFC), Movember Foundation, Prostate Cancer UK, US Department of Defense, Prostate Cancer Foundation, Stand Up To Cancer, Cancer Research UK, UK Department of Health through an Experimental Cancer Medicine Centre grant, Seed Funding Program of Rowan University, Medical Research Council, Academy of Medical Sciences, Prostate Cancer UK, NCI, National Cancer Institute Early Detection Research Network, Prostate Cancer Canada, Movember Prostate Cancer Canada Rising Star Award, Canadian Institutes of Health Research (CIHR), Terry Fox Research Institute (TFRI) New Investigator Awards, Wilson Foundation, Mimi and John Cole Foundation.

The news reporters obtained a quote from the research from the University of Texas Southwestern Medical Center, “We discovered thousands of enhancer-promoter, enhancer-enhancer, as well as promoter-promoter chromatin interactions. These transcriptional hubs operate within the framework set by structural proteins - CTCF and cohesins - and are regulated by the cooperative action of master transcription factors, such as the androgen receptor (AR) and FOXA1. By combining analyses from metastatic castration-resistant PCa (mCRPC) specimens. we show that AR locus amplification contributes to the transcriptional upregulation of the AR gene by increasing the total number of chromatin interaction modules comprisingthe AR gene and its distal enhancer. We deconvoluted the transcription control modules of several PCa genes, notably the biomarker KLK3, lineage-restricted genes (KRT8, KRT18, HOXB13, FOXA1, Z8T816), the drug target EZH2, and the oncogene MYC. By integrating clinical PCa data, we defined a germline-somatic interplay between the PCa risk allele rs684232 and the somatically acquired TMPRSS2-ERG gene fusion in the transcriptional regulation of multiple target genes - VR553, FAM57A, and LEMMA.”

According to the news reporters, the research concluded: “Our studies implicate changes in genome organization as a critical determinant of aberrant transcriptional regulation in PCa.”

This research has been peer-reviewed.

For more information on this research see: The Landscape of Rna Polymerase Ii-associated Chromatin Interactions In Prostate Cancer. Journal of Clinical Investigation, 2020;130(8):3987-4005. Journal of Clinical Investigation can be contacted at: Amer Soc Clinical Investigation Inc, 2015 Manchester Rd, Ann Arbor, MI 48104, USA.

Our news correspondents report that additional information may be obtained by contacting Ram S. Mani, University of Texas Southwestern Medical Center, Dept. of Pathology, 5323 Harry Hines Blvd, NB6-444, Dallas, TX 75390, United States. Additional authors for this research include Susmita G. Ramanand, Jiapei Yuan, GuemHee Baek, Yunpeng Gao, Adam Aslam, Nida Safdar, Yong Chen, Kelly Daescu, Michael Q. Zhang, Maryou B. K. Lambros, Suzanne Carreira, Wei Yuan, Adam Sharp, Alec Paschalis, Johann de Bono, Kathleen E. Houlahan, Paul C. Boutros, Chao Xing, Mohammed Kanchwala, Xiaowei Zhan and Ganesh Raj.

The direct object identifier (DOI) for that additional information is: This DOI is a link to an online electronic document that is either free or for purchase, and can be your direct source for a journal article and its citation.

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