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Prostate cancer (PCa) is one of the most common cancers and the second leading cause of cancer-related death in the U.S. (American Cancer Society, 2017). While treatment strategies for PCa rely primarily on radical prostatectomy (RP), more than one-third of men receiving this treatment experience relapse of the cancer phenotype. Also known as biochemical recurrence, this relapse is defined by a PSA rise of >.2 ng/mL at least twice, or clinical progression demonstrated by local, regional, or distant recurrence as noted via imaging (CT, PET, or bone scan) (Bell, 2015). Patients experiencing this biochemical failure therefore require salvage radiation therapy (RT), a form of treatment given after disease recurrence (Uchio, 2010). However, a small subset of these patients experience a second biochemical recurrence after receiving salvage RT. These patients therefore represent a high-risk cohort with aggressive biological disease, which cannot be predicted with current clinical standards. This creates a lack of optimized treatment strategies to prevent under-treatment in patients with aggressive disease and over-treatment in patients who will not benefit from additional therapy but suffer toxic side effects. Our group previously identified nine microRNAs (miRNAs) that could predict biochemical recurrence after salvage RT in a cohort of PCa patients (n=43) (Bell, 2015). As predictive biomarkers, these miRNAs could provide a method of identifying and classifying patients based on response to RT. Of these, miR-628-3p, miR-320e, miR-508-3p, miR-598, miR-601, and miR-563 have been shown to play a role in PCa while miR-1193, miR-4516, and miR-626 are novel in PCa but linked to roles in other cancers (Srivastava, 2014; Hsieh 2013; Peng, 2011; Corcoran, 2014; Hessvik, 2012; Haj-Ahmad, 2014; Chowdhari, 2014; Riaz, 2013; Li, 2016). To our knowledge, there are not yet any publications indicating a role for any of these nine miRNAs in radiation resistance. The purpose of this study is to identify pathways of radiation resistance in PCa and characterize miRNAs previously linked to biochemical failure after salvage RT. We hypothesized that miRNAs previously identified to be predictive of salvage RT response may play a role in radiation resistance or cancer progression. Seven previously identified miRNAs were screened in vitro to determine their possible mechanism(s) in radiation resistance. Of these seven miRNAs implicated in PCa radiation resistance, miR-508-3p and miR-1193 were consistently correlated with tumor inhibitory effects; both miR-508-3p and miR-1193 decreased cell proliferation, cell viability, and inhibited colony formation in response to radiation. These miRNAs therefore represent potential therapeutic targets that provide insight to the mechanisms of cancer progression in PCa patients.