Abstract 3060: MicroRNA expression profiling in African American and Caucasian prostate cancer.

PURPOSE: African American men have almost twice the incidence and death rates related to prostate cancer compared to Caucasian men. Several studies have suggested that some of these differences may be attributed to the elevated expression of different genes. Recently, a new class of genetic regulators has emerged known as microRNAs. Many reports have found microRNAs to be implicated in cell growth, cell differentiation and the onset of many diseases including prostate cancer. We sought to investigate whether microRNAs are differentially expressed in African American and Caucasian prostate samples. METHODS: We analyzed the expression of over 300 microRNAs in 11 African American and Caucasian cell lines utilizing Affymetrix Microarray Chip. Validations of the most significant miRNAs were done by qRT-PCR. Methylation analysis of miR-152 promoter region was carried out by performing bisulfite modification and DNA sequencing. Characterization of the miRNA was carried out by performing MTT assay, Flow Cytometry, Western Blot, and Imunoflourescence. RESULTS: We identified 15 microRNAs that were differentially expressed between the African American and Caucasian cell lines. Further validations led to the identification of miR-152 which is significantly expressed among both groups. Bisulfite modification and DNA sequencing revealed that miR-152 is methylated in aggressive prostate cancer cell lines. 5-Aza-2’/TSA treatment restored miR-152 levels in these cell lines. MiR-152 is responsible for inhibiting DNA methyltransferase 1, Rictor and TGF-β. Our results showed that miR-152 reduced cellular proliferation in PC-3, DU-145 and LNCaP prostate cancer cell lines. In addition, miR-152 initiated G2-M cell cycle arrest. Expression of miR-152 in 40 normal-tumor paired prostate tissue samples indicated that its expression was down-regulated in 67% of tumor samples. Analysis of African American and Caucasian prostate normal-tumor paired sample revealed that both normal and tumor prostate samples had lower miR-152 expression in the African American prostate samples compared to the Caucasian prostate samples. CONCLUSION: These results give evidence that microRNAs may play a role in the advance progression seen in prostate cancer in African Americans. Future studies will focus on validating these results in larger patient sample sizes. Research supported by G12 RR03059-21A1(NIH/RCMI), and CA118623 (NIH/NCI). Citation Format: Shaniece Theodore, Melissa Davis, Jhong Rhim, William Grizzle, Timothy Turner, Clayton Yates. MicroRNA expression profiling in African American and Caucasian prostate cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3060. doi:10.1158/1538-7445.AM2013-3060