Abstract B03: PVT1 exon 9 is a potential non-invasive biomarker that regulates apoptosis and the cell cycle in aggressive prostate cancer in black males

Abstract

Abstract Prostate cancer (PCA) is the most common non-skin cancer and the second leading cause of cancer-related death for men in the U.S. Black males have a higher incidence of PCA, compared to White males. In fact, Black race is a confirmed, non-modifiable risk factor for PCA with a 2.5 fold greater risk of lethal PCA compared to Caucasian males. Discovery of effective early detection strategies are necessary to address the profound health disparity. The chromosomal region 8q24 is associated with aggressive PCA in Black men and variants of this region have been identified to interact with the PVT1 non-protein coding gene in PCA. PVT1 is located at 8q24 and is transcribed into a long non-protein coding RNA that has been implicated in PCA. Using a panel of eight prostate epithelial cell lines modeling a variety of clinical characteristics of PCA, we investigated the expression of 12 exons of PVT1 in PCA. We discovered that exon 9 of PVT1 is consistently significantly upregulated (by about 2-folds) in aggressive PCA cell lines derived from Black males (MDA PCa 2b and E006AA-hT) in comparison to indolent PCA cells from a Black male E006AA, and both indolent and aggressive PCA cell lines derived from White males. Cell-free PVT1 exon 9 was detectable in cell culture medium, and found to be detectable at significantly higher levels from the aggressive E006AA-hT cell line in comparison to the indolent E006AA cell line from which it was derived. PVT1 exon 9 was efficiently silenced by a custom-designed siRNA. We observed that silencing of PVT1 exon 9 expression resulted in apoptosis and cell cycle arrest at G1 phase in the MDA PCa 2b cell line derived from a Black male. Consequently, PVT1 exon 9 may regulate apoptosis and the cell cycle in aggressive PCA in Black males. Our ability to detect cell-free PVT1 exon 9 indicates that PVT1 exon 9 may have potential future role in non-invasive early detection of aggressive PCA in Black males. Citation Format: Adeodat Ilboudo, Dibash Das, Olorunseun O. Ogunwobi. PVT1 exon 9 is a potential non-invasive biomarker that regulates apoptosis and the cell cycle in aggressive prostate cancer in black males. [abstract]. In: Proceedings of the Eighth AACR Conference on The Science of Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; Nov 13-16, 2015; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2016;25(3 Suppl):Abstract nr B03.