Department of Oncology, The First Affiliated Hospital, Nanjing Medical University, Nanjing, China.
Department of Radiation Oncology, Huai'an First People's Hospital, Nanjing Medical University, Huai'an, China.
J Cell Biochem. 2018 Mar;119(3):2787-2796. doi: 10.1002/jcb.26447. Epub 2017 Dec 4.
LncRNAs and microRNAs can play significant roles in various cancers, including gastric cancer (GC). In our study, we investigated the role of lncRNA XIST in GC. We observed that XIST was increased in MGC803 and BGC823 cells compared to human normal gastric epithelial GES-1 cells. It was also shown that miR-185 was decreased in GC cell lines. Silencing XIST can inhibit the growth of GC cells and bioinformatics analysis was performed to confirm the correlation between XIST and miR-185. Interestingly, a negative correlation was indicated between XIST and miR-185 in GC cells. In addition, TGF-β1 was predicted as a target gene of miR-185. miR-185 can modulate TGF-β1 expression negatively in vitro. Moreover, we found that sh-XIST inhibited GC development via decreasing TGF-β1 by upregulating miR-185 in vitro. Therefore, we speculated that XIST can act as a competing endogenous lncRNA (ceRNA) to regulate TGF-β1 by sponging miR-185 in GC. Taken these together, it was indicated that XIST/miR-185/TGF-β1 axis participated in the development of GC. XIST could act as a potential prognostic biomarker in GC development.
长链非编码 RNA(lncRNA)和 microRNA(miRNA)在各种癌症中都发挥着重要作用,包括胃癌(GC)。在本研究中,我们研究了 lncRNA XIST 在 GC 中的作用。我们观察到,与人类正常胃上皮细胞 GES-1 相比,MGC803 和 BGC823 细胞中 XIST 的表达增加。此外,GC 细胞系中 miR-185 的表达降低。沉默 XIST 可以抑制 GC 细胞的生长,并通过生物信息学分析证实 XIST 与 miR-185 之间的相关性。有趣的是,GC 细胞中 XIST 和 miR-185 之间呈负相关。此外,TGF-β1 被预测为 miR-185 的靶基因。miR-185 可以在体外负调控 TGF-β1 的表达。此外,我们发现 sh-XIST 通过上调 miR-185 抑制体外 GC 的发展,从而降低 TGF-β1 的表达。因此,我们推测 XIST 可以作为竞争性内源 RNA(ceRNA),通过海绵吸附 miR-185 来调节 TGF-β1,从而参与 GC 的发生发展。综上所述,XIST/miR-185/TGF-β1 轴参与了 GC 的发生发展。XIST 可能作为 GC 发展的潜在预后生物标志物。