Abstract 4034: Disease- and race-related differences in microRNAs and zinc transporter 1 in human prostate tissue

Background: Prostate cancer (PCa) is the second leading cause of male cancer related deaths. Zn has a protective role against cancer development: the normal peripheral zone glandular epithelium accumulates the mineral, whereas prostatic malignant cells do not. Human Zn transporter 1 (hZIP1) is an important protein involved in Zn accumulation. hZIP1 mRNA expression was shown to be down-regulated in PCa glands that still have intact hZIP1 DNA. Africans, who may have genetically down regulated their Zn absorption capacity in order to prevent toxicity due to high environmental concentrations, are disproportinally affected by PCa. miRNAs have emerged as an important class of post-transcriptional regulators of gene expression. Our hypothesis states that PCa cells express higher level of hZIP1-targeted miRNAs and that African-American patients have higher levels of hZIP1-targeted miRNAs as compared to matched Caucasians patients. Design: We identified putative miRNAs that target the 3′UTR of hZIP1 with bioinformatics and then compared them with published data sets showing miRNA changes that occur in PCa tissue. From this screen, we selected six miRNAs to test: miR-96, miR-223, miR-346, miR-30c, miR-100 and miR-182. We used laser-capture-microdissected (LCM) normal and tumor prostate tissues collected from 10 patients, five Caucasian-American and five African-American. MiRNA and mRNA levels were measured by qRT-PCR with Taqman™ assays. We compared the levels of hZIP1 specific miRNAs between African American and Caucasian in both normal and PCa samples. Results: In normal prostate tissues, 4 (miR-100, miR-182, miR-30 and miR-223) of the tested putative miRNAs showed a trend for elevated levels in African American patients as compared to Caucasians. In both races miR-30c, miR-346, and miR-223 levels were significantly lower in PCa samples when compared to normal tissues. Although the above putative hZIP1-targeted miRNAs were not increased in cancer, the hZIP1 mRNA was lower in the adenocarcinoma samples, confirming previous reports. MiR-182 was the only miRNA significantly increased in PCa in both Caucasian and African-American patients. Correlation studies revealed in fact that miR-182 had perfect inverse correlation with hZIP1 mRNA and the correlation was only present in the samples from Caucasian patients. Conclusions Our screen for putative hZIP1 specific miRNAs revealed miR-182 as a likely regulator of hZIP1 in human prostate. Ongoing experiments are validating hZIP1 as a miR-182 target in vitro. MiR-100, miR-30 and miR-223, although increased in African-Americans, did not show any correlation to hZIP1 mRNA. However, hZIP1 protein level may be affected and is currently being analyzed in our lab. If these miRNAs prove to be unrelated to hZIP1, they may still predispose this population group to PCa by regulating other mechanisms involved in carcinogenesis. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4034.