Abstract B02: miR-1207-3p as a potential prostate cancer biomarker in Black males

Abstract

Abstract African ancestry is an established non-modifiable risk factor for prostate cancer (PCA). Black males are more than twice as likely to be diagnosed with PCA and more likely to have aggressive PCA which increases the likelihood of mortality. To decrease this excess mortality, effective early detection and therapeutic strategies are required. In turn, rational design of early detection and therapeutic strategies requires a clear understanding of PCA tumor biology. The objective of this study was to determine if miR-1207-3p encoded by the PVT1 non-protein coding gene located at the 8q24 PCA susceptibility locus plays a role in PCA biology in Black males. Using a panel of seven PCA cell lines (four derived from White males, and three derived from Black males), we discovered that two of the three PCA cell lines from Black males have the least expression of miR-1207-3p, and that overall, the PCA cell lines from Black males have less miR-1207-3p expression than PCA cell lines from White males. Also, miR-1207-3p expression is comparable in both indolent and aggressive cellular models of PCA derived from Black males, suggesting that loss of miR-1207-3p may already be present in early PCA. miR-1207-3p significantly inhibits proliferation, while inhibition of miR-1207-3p promotes proliferation in all three PCA cell lines derived from Black men (MDA PCa 2b, E006AA, E006AA-hT). Interestingly, analysis of cell-free miR-1207-3p detectable in cell culture medium revealed that 90% less cell-free miR-1207-3p is detectable from the aggressive E006AA-hT PCA cell lines when compared to the indolent E006AA PCA cell line. This suggests that cell-free miR-1207-3p may be able to distinguish indolent from aggressive PCA in Black males. Fibronectin type III domain containing 1 (FNDC1), a domain of fibronectin (FN1), was confirmed as a direct molecular target of miR-1207-3p via Luc-Pair™ Duo-Luciferase assay system. Forced expression of miR-1207-3p led to the suppression of activity of the luciferase reporter gene fused to the FNDC1 3'UTR by about 60% in MDA PCa 2b cells. FNDC1 protein expression is also significantly overexpressed in the three PCA cell lines from Black males. Using western blotting, we also observed that FNDC1, FN1, and AR are overexpressed in the PCA cell lines from Black males when compared to those from White males. Next, we discovered that forced expression of miR-1207-3p significantly inhibited the protein expression of FN1 and FNDC1 by approximately 50% and 85%, respectively. Also, FNDC1 siRNA inhibited the protein expression of FN1 and FNDC1 by nearly 50% for both. Thus, miR-1207-3p regulates FNDC1/FN1/AR molecular pathway in PCA cells derived from Black males. Silencing of FNDC1 by the FNDC1 siRNA resulted in inhibition of cell proliferation. In conclusion, we have discovered a novel miR-1207-3p-dependent FNDC1/FN1/AR molecular pathway that regulates proliferation of PCA cells derived from Black males. Consequently, miR-1207-3p may be a biomarker in PCA with potential clinical applications in Black males. Citation Format: Dibash Kumar Das, Adeodat Ilboudo, Olorunseun O. Ogunwobi. miR-1207-3p as a potential prostate cancer biomarker 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 B02.