Downregulation of miR-141-3p promotes bone metastasis via activating NF-κB signaling in prostate cancer

Background: clinically,prostate cancer (pca) exhibits a high avidity to metastasize to bone. mir-141-3p is an extensively studied mirna in cancers and downregulation 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 are 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 reduced in bone metastatic pca tissues compared with non-bone metastatic pca tissues. low expression 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 effect. 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. © 2017 the author(s).