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

作者: Mi-die Xu , Yiqin Wang , Weiwei Weng , Ping Wei , Peng Qi

DOI: 10.1158/1078-0432.CCR-16-0742

关键词:

摘要: Purpose: The long, noncoding RNA (lncRNA) PVT1 is an important epigenetic regulator with a critical role in human tumors. Here, we aimed to investigate the clinical application and potential molecular mechanisms of gastric cancer tumorigenesis progression.Experimental Design: expression level was determined by RT-qPCR analysis 190 pairs tissues adjacent normal mucosa (ANT). biologic functions were assessed vitro vivo functional experiments. protein pull-down assays LS/MS mass spectrometry performed detect identify PVT1- interacting FOXM1. Protein-RNA immunoprecipitation conducted examine interaction FOXM1 Chromatin (ChIP) luciferase analyses utilized binding site on promoter.Results: lncRNA significantly upregulated compared ANTs. High predicted poor prognosis patients cancer. enhanced cell proliferation invasion vivoPVT1 directly bound increased posttranslationally. Moreover, also FOXM1-responsive lncRNA, binds promoter activate its transcription. Finally, fulfilled oncogenic FOXM1-mediated manner.Conclusions: Our study suggests that promotes tumor progression may be valuable prognostic predictor for cancer, positive feedback loop PVT1-FOXM1 could therapeutic target pharmacologic strategies. Clin Cancer Res; 23(8); 2071-80. ©2016 AACR.

参考文章(29)
Ping Wei, Mi Die Xu, Xiang Du, Yi Qin Wang, Yu Si Yang, Wei Wei Weng, BCL6 is a negative prognostic factor and exhibits pro-oncogenic activity in ovarian cancer. American Journal of Cancer Research. ,vol. 5, pp. 255- 266 ,(2015)
Peng Qi, Mi-die Xu, Xiao-Han Shen, Shu-Juan Ni, Dan Huang, Cong Tan, Wei-Wei Weng, Wei-Qi Sheng, Xiao-Yan Zhou, Xiang Du, Reciprocal repression between TUSC7 and miR-23b in gastric cancer. International Journal of Cancer. ,vol. 137, pp. 1269- 1278 ,(2015) , 10.1002/IJC.29516
Patrick Tan, Khay-Guan Yeoh, Genetics and Molecular Pathogenesis of Gastric Adenocarcinoma. Gastroenterology. ,vol. 149, pp. 1153- 1162 ,(2015) , 10.1053/J.GASTRO.2015.05.059
Jian Ding, Dan Li, Minzhen Gong, Jinpo Wang, Xunru Huang, Ting Wu, Chengdang Wang, Expression and clinical significance of the long non-coding RNA PVT1 in human gastric cancer. OncoTargets and Therapy. ,vol. 7, pp. 1625- 1630 ,(2014) , 10.2147/OTT.S68854
Hui Cai, Jingde Chen, Bin He, Qiang Li, Yandong Li, Yong Gao, A FOXM1 related long non-coding RNA contributes to gastric cancer cell migration. Molecular and Cellular Biochemistry. ,vol. 406, pp. 31- 41 ,(2015) , 10.1007/S11010-015-2421-3
Yuen-Yi Tseng, Branden S. Moriarity, Wuming Gong, Ryutaro Akiyama, Ashutosh Tiwari, Hiroko Kawakami, Peter Ronning, Brian Reuland, Kacey Guenther, Thomas C. Beadnell, Jaclyn Essig, George M. Otto, M. Gerard O’Sullivan, David A. Largaespada, Kathryn L. Schwertfeger, York Marahrens, Yasuhiko Kawakami, Anindya Bagchi, PVT1 dependence in cancer with MYC copy-number increase Nature. ,vol. 512, pp. 82- 86 ,(2014) , 10.1038/NATURE13311
Mi-die Xu, Lei Dong, Peng Qi, Wei-wei Weng, Xiao-han Shen, Shu-juan Ni, Dan Huang, Cong Tan, Wei-qi Sheng, Xiao-yan Zhou, Xiang Du, Pituitary tumor-transforming gene-1 serves as an independent prognostic biomarker for gastric cancer. Gastric Cancer. ,vol. 19, pp. 107- 115 ,(2016) , 10.1007/S10120-015-0459-2
Pradip Raychaudhuri, Hyun Jung Park, FoxM1: A Master Regulator of Tumor Metastasis Cancer Research. ,vol. 71, pp. 4329- 4333 ,(2011) , 10.1158/0008-5472.CAN-11-0640
M Maurizi, G Ferrandina, G Almadori, G Scambia, G Cadoni, G D'Agostino, FG Serra, M Piantelli, S Mancuso, FO Ranelletti, Prognostic significance of methyl- p -hydroxy-phenyllactate-esterase activity in laryngeal squamous cell carcinoma British Journal of Cancer. ,vol. 77, pp. 1253- 1259 ,(1998) , 10.1038/BJC.1998.210