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Background: Clinically, prostate cancer (PCa) exhibits a high avidity to metastasize to bone.miR-141-3p is an extensively studied miRNA in cancers and downexpression of miR-141-3p has been widely reported to be involved in the progression and metastasis of several human cancer types.However, the clinical significance and biological roles of miR-141-3p in bone metastasis of PCa is still unclear.Methods: miR-141-3p expression was examined in 89 non-bone metastatic and 52 bone metastatic PCa tissues by real-time PCR.Statistical analysis was performed to investigate the clinical correlation between miR-141-3p expression levels and clinicopathological characteristics in PCa patients.The biological roles of miR-141-3p in bone metastasis of PCa were evaluated both in vitro and a mouse intracardial model in vivo.Bioinformatics analysis, western blot, luciferase reporter and miRNA immunoprecipitation assays were performed to explore and examine the relationship between miR-141-3p and its potential targets.Clinical correlation of miR-141-3p with its targets was examined in clinical PCa tissues.Results: miR-141-3p expression is repressed in bone metastatic PCa tissues compared with non-bone metastatic PCa tissues.Downexpression of miR-141-3p positively correlates with serum PSA levels, Gleason grade and bone metastasis status in PCa patients.Furthermore, upregulating miR-141-3p suppresses the EMT, invasion and migration of PCa cells in vitro.Conversely,silencing miR-141-3p yields an opposite effects.Importantly, upregulating miR-141-3p dramatically reduces bone metastasis of PC-3 cells in vivo.Our results further show that miR-141-3p inhibits the activation of NF-κB signaling via directly targeting tumor necrosis factor receptor-associated factor 5(TRAF5) and 6 (TRAF6), which further suppresses invasion, migration and bone metastasis of PCa cells.The clinical negative correlation of miR-141-3p expression with TRAF5, TRAF6 and NF-κB signaling activity is demonstrated in PCa tissues.Conclusion: our findings unravel a novel mechanism underlying the bone metastasis of PCa, suggesting that miR-141-3p mimics might represent a potential therapeutic avenue for the treatment of PCa bone metastasis.