Medical Oncology, First Affiliated Hospital of Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi Province, 710061, China; Radiotherapy Department, Shaanxi Provincial Tumor Hospital, Affiliated Hospital of Medical College of Xi'an Jiaotong University, Xi'an, Shaanxi Province, 710061, China.
Department of Oncology, The First People's Hospital of Xianyang, Xianyang, Shaanxi Province, 712000, China.
Chem Biol Interact. 2019 May 1;304:1-9. doi: 10.1016/j.cbi.2019.02.026. Epub 2019 Mar 1.
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.
核糖体蛋白 S15A（RPS15A）已成为多种人类癌症的新型癌基因。然而，RPS15A 是否参与胰腺癌尚不清楚。在这项研究中，我们旨在研究 RPS15A 在胰腺癌中的潜在相关性，并阐明其潜在的调节机制。我们发现 RPS15A 在胰腺癌细胞系中表达明显上调。RPS15A 敲低导致胰腺癌细胞增殖和集落形成减少，并诱导细胞周期停滞在 G0/G1 期。此外，RPS15A 敲低下调 β-连环蛋白表达并阻断 Wnt 信号通路的激活。值得注意的是，RPS15A 是 microRNA-519d-3p（miR-519d-3p）的靶基因，miR-519d-3p 是一种肿瘤抑制 miRNA。进一步的数据表明，miR-519d-3p 负调控胰腺癌细胞中 RPS15A 的表达。此外，miR-519d-3p 在胰腺癌细胞系和组织中的表达显著降低，与 RPS15A 的表达呈负相关。miR-519d-3p 的过表达显著抑制胰腺癌细胞的增殖和 Wnt/β-连环蛋白信号通路，模拟 RPS15A 敲低的相似作用。然而，RPS15A 表达的恢复部分逆转了 miR-519d-3p 的抗肿瘤作用。总之，我们的研究结果表明，RPS15A 敲低或 miR-519d-3p 抑制 RPS15A 表达抑制与 Wnt/β-连环蛋白信号通路抑制相关的胰腺癌细胞生长。我们的研究表明，miR-519d-3p/RPS15A/Wnt/β-连环蛋白调控轴在胰腺癌的进展中起着重要作用，可能成为胰腺癌治疗的潜在靶点。
