Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, China.
Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
Clin Cancer Res. 2017 Apr 15;23(8):2071-2080. doi: 10.1158/1078-0432.CCR-16-0742. Epub 2016 Oct 18.
The long, noncoding RNA (lncRNA) is an important epigenetic regulator with a critical role in human tumors. Here, we aimed to investigate the clinical application and the potential molecular mechanisms of in gastric cancer tumorigenesis and progression. The expression level of was determined by RT-qPCR analysis in 190 pairs of gastric cancer tissues and adjacent normal gastric mucosa tissues (ANT). The biologic functions of were assessed by and functional experiments. RNA protein pull-down assays and LS/MS mass spectrometry analysis were performed to detect and identify the interacting protein FOXM1. Protein-RNA immunoprecipitation assays were conducted to examine the interaction of FOXM1 and Chromatin immunoprecipitation (ChIP) and luciferase analyses were utilized to identify the binding site of FOXM1 on the promoter. The lncRNA was significantly upregulated in gastric cancer tissues compared with ANTs. High expression of predicted poor prognosis in patients with gastric cancer. enhanced gastric cancer cell proliferation and invasion and directly bound FOXM1 protein and increased FOXM1 posttranslationally. Moreover, is also a FOXM1-responsive lncRNA, and FOXM1 directly binds to the promoter to activate its transcription. Finally, fulfilled its oncogenic functions in a FOXM1-mediated manner. Our study suggests that promotes tumor progression by interacting with FOXM1. may be a valuable prognostic predictor for gastric cancer, and the positive feedback loop of -FOXM1 could be a therapeutic target in pharmacologic strategies. .
长非编码 RNA（lncRNA）是一种重要的表观遗传调节剂，在人类肿瘤中具有关键作用。在这里，我们旨在研究 lncRNA 在胃癌发生和发展中的临床应用和潜在分子机制。通过 RT-qPCR 分析在 190 对胃癌组织和相邻正常胃黏膜组织（ANT）中测定 lncRNA 的表达水平。通过 和 功能实验评估 lncRNA 的生物学功能。进行 RNA 蛋白下拉测定和 LS/MS 质谱分析以检测和鉴定 相互作用蛋白 FOXM1。进行蛋白-RNA 免疫沉淀测定以检查 FOXM1 和 的相互作用。进行染色质免疫沉淀（ChIP）和荧光素酶分析以鉴定 FOXM1 在 启动子上的结合位点。与 ANTs 相比，lncRNA 在胃癌组织中显著上调。lncRNA 的高表达预示着胃癌患者预后不良。 增强了胃癌细胞的增殖和侵袭能力，并且直接结合 FOXM1 蛋白并增加 FOXM1 翻译后。此外， 也是 FOXM1 反应性 lncRNA，FOXM1 直接结合到 启动子上以激活其转录。最后， 通过 FOXM1 介导的方式发挥其致癌功能。我们的研究表明， 通过与 FOXM1 相互作用促进肿瘤进展。 可能是胃癌有价值的预后预测指标，并且 -FOXM1 的正反馈环可能是药物策略中的治疗靶点。
