Circulating Prognostic and Tissue-Specific microRNAs in Prostate Cancer

Prostate cancer has the highest incidence and second highest mortality rate for men in the United States. Even with this large disease burden, screening and treatment of prostate cancer has become controversial due to the overtreatment of indolent disease. Determining which prostate cancers will progress and which will not has become essential to patient care. Herein, microRNAs (miRs) were examined in the serum and serum extracellular vesicles (EVs) of prostate cancer patients prior to treatment as prognostic markers for disease outcome. MiRs within serum and serum EVs were determined to be significantly associated with biopsy Gleason grade group and adverse pathology, which are surrogate endpoints for aggressive disease. The goal of this work is to develop a noninvasive serum test that would classify patients with indolent cancer, which would help prevent the overtreatment of nonlethal cancer. In addition to their biomarker potential, microRNAs are a type of small noncoding RNA involved in regulating mRNA translation in cells. MicroRNA expression goes awry in prostate cancer and can have oncogenic or tumor suppressor roles in cancer progression. The microRNA profiles of patient-derived prostate epithelial and stromal cells were characterized, and the function of a specific microRNA (microRNA-199a) was further investigated in this thesis. MicroRNA-199a was highly expressed in prostate stromal cells and could be transferred to epithelial cells in a paracrine mechanism and target integrin signaling. The expression of microRNA-199a was decreased in prostate cancer compared to benign tissue, indicating a tumor suppressor function.