PRL-3 promotes gastric cancer migration and invasion through a NF-κB-HIF-1α-miR-210 axis

Phosphatase of regenerating liver-3 (PRL-3) has been implicated in controlling cancer cell invasiveness. Deregulated expression of PRL-3 is involved in cancer progression and predicts poor overall survival. Recent studies have revealed critical roles for microRNAs in various cellular processes, including tumorigenic development. In this study, we aimed to explore the linkage between PRL-3 and microRNAs in gastric cancer. We found that PRL-3 transcript levels were positively correlated with miR-210 levels in gastric cancer tissues. In gastric cancer cells, PRL-3 upregulated miR-210 expression in a HIF-1 alpha-dependent fashion under normoxia and hypoxia. In addition, PRL-3 activated NF-kappa B signaling and promoted HIF-1 alpha expression through modulating phosphorylation of p65. NF-kappa B signaling, HIF-1 alpha, and miR-210 partially contributed to PRL-3-induced migration and invasion. Furthermore, the levels of PRL-3, HIF-1 alpha, and miR-210 transcripts inversely affected the overall survival of gastric cancer patients. Our work identified the existence of a PRL-3-NF-kappa B-HIF-1 alpha-miR-210 axis, thus providing new insight into the role of PRL-3 in promoting gastric cancer invasiveness.