A Positive Feedback Loop of lncRNA- PVT1 and FOXM1 Facilitates Gastric Cancer Growth and Invasion

• Published in: Clinical cancer research Vol. 23; no. 8; pp. 2071 - 2080
• Main Authors: Xu, Mi-Die, Wang, Yiqin, Weng, Weiwei, Wei, Ping, Qi, Peng, Zhang, Qiongyan, Tan, Cong, Ni, Shu-Juan, Dong, Lei, Yang, Yusi, Lin, Wanrun, Xu, Qinghua, Huang, Dan, Huang, Zhaohui, Ma, Yuqing, Zhang, Wei, Sheng, Weiqi, Du, Xiang
• Format: Journal Article
• Language: English
• Published: United States American Association for Cancer Research Inc 15.04.2017
• Subjects: Binding sites; Blotting, Western; Cancer; Cell Proliferation; Chromatin; Chromatin Immunoprecipitation; Disease-Free Survival; Experimental design; Feedback; Feedback loops; Feedback, Physiological; Forkhead Box Protein M1 - biosynthesis; Forkhead Box Protein M1 - genetics; Gastric cancer; Gastric mucosa; Gene Expression Regulation, Neoplastic - genetics; Humans; Immunoprecipitation; Kaplan-Meier Estimate; Mass Spectrometry; Mass spectroscopy; Molecular modelling; Neoplasm Invasiveness - genetics; Neoplasm Invasiveness - pathology; Pharmacology; Positive feedback; Proportional Hazards Models; Proteins; Ribonucleic acid; RNA; RNA, Long Noncoding - genetics; Stomach Neoplasms - genetics; Stomach Neoplasms - mortality; Stomach Neoplasms - pathology; Tissues; Transcription; Tumorigenesis; Tumors; Up-Regulation
• ISSN: 1078-0432; 1557-3265
• DOI: 10.1158/1078-0432.CCR-16-0742

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. .