EPA Modulates KLK Genes via miR-378: A Potential Therapy in Prostate Cancer

SIMPLE SUMMARY: Castration resistant prostate cancer (CRPC) is one of the most pestilent form of prostate cancer (PCa), accounting for approximately 10–20% of all PCas, which carry poor mortality and morbidity rates. The focus in this study is on EPA, a natural supplement commonly found in fish oils. EPA induces the expression of PGC-1β gene and co-expresses miR-378 in cells, a nucleic acid sequence that inhibits PCa cell proliferation. This significance is highlighted in this study as a potential adjunctive therapy for all stages of PCa including CRPC. ABSTRACT: It is known that miRNA-378a-3p (miR-378) could be induced by eicosapentaenoic acid (EPA), an omega-3 fatty acid. Herein, we first demonstrated how miR-378 exerts anti-prostate cancer (PCa) actions by influencing multiple target genes, including KLK2, KLK4, KLK6, and KLK14, which are implicated in PCa development, cell proliferation, and cell survival. Furthermore, these genes also correlate with androgen and mTOR signaling transduction, and are considered pivotal pathways for the onset and progression of PCa. In total, four PCa cell lines and eight pairing tissues (tumor vs. normal) from clinical PCa patients were included in the current study. The results showed high significance after EPA induced tumor cells containing higher expression levels of miR-378, and led the PCa cells having low cell viabilities, and they progressed to apoptosis when compared with normal prostate cells (p < 0.001). The findings indicated that EPA might become a potential therapy for PCa, especially because it is derived from the components of natural fish oil; it may prove to be a great help for solving the problem of castration-resistant prostate cancer (CRPC).