microRNA Associated with Aggressive Prostate Cancer in Racial Disparity.
Hongying Huang, Xinyu Wu, Liye Zhou, Yirong Li, Olca Basturk, Harry Ostrer, Steve Freedland, Iman Osman, Victor Reuter, Jonathan Melamed, Peng Lee. New York University Medical Center, NY; Memorial Sloan Kettering Cancer Center, New York, NY
Background: African American (AA) men have the highest rates of prostate cancer (PCA) in the world and a worse prognosis when compared to Caucasian American (CA) men. The reason for the ethnic disparity between AA and CA men in PCA risk, incidence, clinical progression, and disease specific death includes genetic differences between the two populations. These genetic differences may occur in microRNAs (miRNAs), a class of small, non-coding RNAs regulating the expression of genes, including tumor suppressor genes and oncogenes, at the level of translation. It has been reported that subsets of miRNAs are strongly associated with racial disparity in tumors such as uterine leiomyoma. In this study, we determined the association between altered expression and function of miRNA in prostate cancer, especially in relation to its racial disparity.
Design: To test the hypothesis that altered expression of miRNAs is associated with racial differences in prostate cancer patients, we first examined the expression of miRNAs in benign and cancerous prostate with a miRNA microarray of 700 miRNAs using prostatectomy specimens of AA (n=8) and CA (n=7) PCA. Next, we determined the association of altered miRNA expression on a racial tissue microarray within these two populations (n=71 for AA and n=56 for CA). We also tested whether increased expression of specific miRNAs promotes cell growth, invasion and metastasis in prostate cancer cell lines in vitro by using WST colorimetric cell proliferation and Matrigel invasion assays.
Results: The miRNA microarray analysis of the 15 macrodissected matched benign and cancer tissue revealed differences in distribution of a number of miRNAs in AA versus CA prostate cancer when compared against corresponding expression in benign AA and CA prostate tissue. Among the dysregulated miRNAs, with confirmation by miRNA in-situ hybridization, let7c was decreased in prostate cancer with a greater decrease in AA prostate cancer. We also observed a racial difference for miR30c. Let-7c overexpression in in vitro studies reduced the growth of prostate cancer cells.
Conclusions: Certain miRNA types are associated with prostate cancer in African American patients, and based on biologic function may contribute to aggressive behavior.
Category: Genitourinary (including renal tumors)
Monday, February 28, 2011 1:00 PM
Poster Session II # 134, Monday Afternoon