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  • Title: Overexpression of microRNA-519d-3p suppressed the growth of pancreatic cancer cells by inhibiting ribosomal protein S15A-mediated Wnt/β-catenin signaling.
    Author: Liang J, Liu Y, Zhang L, Tan J, Li E, Li F.
    Journal: Chem Biol Interact; 2019 May 01; 304():1-9. PubMed ID: 30831090.
    Abstract:
    Ribosomal protein S15A (RPS15A) has emerged as a novel oncogene of various human cancers. However, whether RPS15A is involved in pancreatic cancer remains unclear. In this study, we aimed to investigate the potential relevance of RPS15A in pancreatic cancer and elucidate the underlying regulatory mechanism. We found that RPS15A expression was significantly up-regulated in pancreatic cancer cell lines. RPS15A knockdown resulted in a decrease of cell proliferation and colony formation, and induced cell cycle arrest in G0/G1 phases of pancreatic cancer cells in vitro. In addition, RPS15A knockdown down-regulated β-catenin expression and blocked the activation of Wnt signaling. Notably, RPS15A was identified as a target gene of microRNA-519d-3p (miR-519d-3p), a tumor suppressive miRNA. Further data showed that miR-519d-3p negatively regulated RPS15A expression in pancreatic cancer cells. Moreover, miR-591d-3p expression was significantly decreased in pancreatic cancer cell lines and tissues and was inversely correlated with RPS15A expression. The overexpression of miR-519d-3p significantly inhibited the proliferation and Wnt/β-catenin signaling in pancreatic cancer cells, mimicking the similar effect of RPS15A knockdown. However, restoration of RPS15A expression partially reversed the antitumor effect of miR-519d-3p. Taken together, our results demonstrate that RPS15A knockdown or RPS15A inhibition by miR-519d-3p suppresses the growth of pancreatic cancer cells associated with the inhibition of Wnt/β-catenin signaling. Our study suggests that the miR-519d-3p/RPS15A/Wnt/β-catenin regulation axis plays an important role in the progression of pancreatic cancer and may serve as potential targets for treatment of pancreatic cancer.
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