Abstract B64: Race and prostate cancer: miRNA isoforms and tRNA fragments could hold some of the answers

Abstract

Abstract Prostate cancer is the most frequently occurring cancer in men. Compared to White (Wh) men, Black/African American (B/Aa) men exhibit higher mortality and higher incidence rates of prostate cancer. This difference remains even after modifiable factors are taken into account, which suggests an underlying cause. Recent studies greatly improved our understanding of the biochemistry of prostate cancer. Nonetheless, many open questions remain, especially with regard to the molecular underpinnings of the observed race disparities. In this study, we analyzed 526 transcriptomic datasets from prostate adenocarcinoma (PRAD) patients. We obtained the data from The Cancer Genome Atlas (TCGA) repository. We focused on two categories of noncoding RNAs that regulate messenger RNA (mRNA) and protein abundance: (1) microRNAs (miRNAs) and their isoforms (isomiRs) and (2) tRNA-derived fragments (tRFs). Both tRFs and isomiRs regulate mRNAs and their proteins through the RNA induced silencing complex (RISC). Furthermore, tRFs have a number of other regulatory roles in healthy and diseased cells, including direct physical interactions with ribosomal proteins and initiation factors. Notably, we have demonstrated and reported previously that isomiRs and tRFs are constitutive and transcribed in a manner that depends strongly on a person's gender, race, and population origin, as well as on tissue type, tissue state, and disease type/subtype. Our analyses of the TCGA PRAD datasets revealed that both isomiRs and tRFs are disrupted in PRAD. By extension, the regulatory networks that link isomiRs and tRFs to mRNAs are also disrupted. We also uncovered transcriptomic differences and differential regulatory relationships that are aligned with patient race. Moreover, we found that the molecular differences between B/Aa and Wh PRAD patients extend to normal prostate tissue as well. These findings mirror earlier results that we obtained from both healthy individuals and cancer patients. The race-dependent regulatory profiles highlight differences in the underlying biology in B/Aa and Wh individuals that have yet to be explored. For example, the corresponding molecules could potentially be leveraged as novel biomarkers or alternative therapeutic targets. This study represents the first characterization of isomiRs and tRFs in a large cohort of PRAD patients. Citation Format: Rogan G. Magee, Aristeidis G. Telonis, Phillipe Loher, Eric Londin, Isidore Rigoutsos. Race and prostate cancer: miRNA isoforms and tRNA fragments could hold some of the answers [abstract]. In: Proceedings of the Tenth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2017 Sep 25-28; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2018;27(7 Suppl):Abstract nr B64.