Department of Oncology, Suizhou Hospital, Hubei University of Medicine, Suizhou, Hubei, 441399, China.
Department of ICU, Suizhou Hospital, Hubei University of Medicine, Suizhou, Hubei, 441399, China.
Biomed Pharmacother. 2018 Aug;104:383-389. doi: 10.1016/j.biopha.2018.05.064. Epub 2018 May 25.
This work aims to explore the roles and related mechanisms of RNA binding protein Lin28B in gastric cancer cells stemness. We found that Lin28B expression was negatively correlated with the overall survival (OS) of gastric cancer patients, and significantly increased in gastric cancer cells compared with that in gastric epithelial cells. Lin28B overexpression increased spheroid formation, expression of gastric cancer stemness-related markers, and decreased cisplatin sensitivity in gastric cancer cells. Mechanistically, Lin28B could directly bind to NRP-1 3'UTR, thus increasing NRP-1 mRNA stability and expression, and activate the downstream Wnt/β-catenin signaling. Knockdown of NRP-1 or treatment with Wnt/β-catenin antagonist could rescue the promotive effects of Lin28B on gastric cancer stemness. Thus, thes results indicate that Lin28B could facilitate gastric cancer stemness via directly binding to NRP-1 3'UTR and activating the downstream Wnt/β-catenin signaling.
本研究旨在探讨 RNA 结合蛋白 Lin28B 在胃癌细胞干性中的作用及其相关机制。我们发现，Lin28B 的表达与胃癌患者的总生存期（OS）呈负相关，并且在胃癌细胞中明显高于胃上皮细胞。Lin28B 的过表达增加了胃癌细胞球体的形成、胃癌干细胞相关标志物的表达，并降低了顺铂的敏感性。机制上，Lin28B 可以直接结合 NRP-1 3'UTR，从而增加 NRP-1 mRNA 的稳定性和表达，并激活下游的 Wnt/β-catenin 信号通路。NRP-1 的敲低或 Wnt/β-catenin 拮抗剂的处理可以挽救 Lin28B 对胃癌干细胞的促进作用。因此，这些结果表明，Lin28B 可以通过直接结合 NRP-1 3'UTR 并激活下游的 Wnt/β-catenin 信号通路促进胃癌干细胞的干性。
