Poster abstracts
Poster number 53 submitted by Samantha Gargasz
Post-Transcriptional Regulation of AR Variant 7 in Castration-Resistant Prostate Cancer
Samantha Gargasz (Cleveland State University, Department of Biological, Geological, and Environmental Sciences), Luca Argentieri (Cleveland State University, Department of Biological, Geological, and Environmental Sciences), Girish C. Shukla (Cleveland State University, Center For Gene Regulation in Health and Disease, Department of Biological, Geological, and Environmental Science)
Abstract:
Prostate cancer (PCa) is the most commonly diagnosed cancer in males in the United States and the second leading cause of cancer-related death, with up to 50% of cases progressing to a metastatic, therapy-resistant stage of disease. Thus, the discovery of novel molecules involved in the progression of this disease is needed to uncover potential therapeutic strategies to combat tumors resistant to current treatment options. The long-noncoding RNA, ARLNC1, was first discovered due to its prostate-tumor-specific expression and interaction with the androgen receptor (AR), a major driver of PCa growth and progression. In PCa, ARLNC1 binds within the 3’ untranslated region (UTR) of the full-length AR mRNA, resulting in AR overexpression. This causes accelerated tumor growth and development. ARLNC1 has been demonstrated to regulate AR in a positive feedback loop. Recently, potential interactions between ARLNC1 and AR-V7, a splice variant of AR that arises in response to certain PCa treatments, have been uncovered through in silico sequence analysis. These putative interactions have been supported by in vitro studies suggesting that certain regions of the AR-V7 3’UTR could provide an interaction site for ARLNC1. The below experiments explore these interactions and propose a mechanism by which ARLNC1 also regulates AR-V7 expression in castration-resistant prostate cancer, though the details of this interaction have yet to be uncovered. The post-transcriptional landscape of castration-resistant prostate tumors expressing AR-V7 has not yet been investigated. We hypothesize that AR-V7 mRNA is controlled by a diverse post-transcriptional landscape of non-coding RNAs. Exploring the role of ARLNC1 and its role in the regulation of AR-V7 expression and activity will uncover novel molecular mechanisms contributing to PCa progression, providing potential therapeutic targets for the development of treatment strategies to combat castration-resistant disease.
References:
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2. Teo MY, Rathkopf DE, Kantoff P. 2019. Treatment of advanced prostate cancer. Annu Rev Med. 70:479-499.
3. Scher HI, Sawyers CL. 2005. Biology of progressive, castration-resistant prostate cancer: Directed therapies targeting the androgen-receptor signaling axis. J Clin Oncol. 23(32):8253-8261.
Keywords: Prostate Cancer, non-coding RNA, 3UTR