miR-1, regulated by LMP1, suppresses tumour growth and metastasis by targeting K-ras in nasopharyngeal carcinoma

被引:30
作者
Chen, Xi [1 ]
Shi, Jingxuan [1 ]
Zhong, Jianwen [1 ]
Huang, Zhenyun [1 ]
Luo, Xi [1 ]
Huang, Yaping [1 ]
Feng, Shuang [1 ]
Shao, Jianbo [1 ]
Liu, Dabo [1 ]
机构
[1] Guangzhou Med Univ, Guangzhou Women & Childrens Med Ctr, Dept Otorhinolaryngol, 318 Renmin Zhong Rd, Guangzhou 510120, Guangdong, Peoples R China
关键词
EBV; K-ras; LMP1; miR-1; nasopharyngeal carcinoma; DOWN-REGULATION; CANCER; GENE; EXPRESSION; APOPTOSIS; INVASION; MUTATION; KRAS;
D O I
10.1111/iep.12162
中图分类号
R36 [病理学];
学科分类号
100104 ;
摘要
There is evidence to show that downregulation of miR-1 expression is closely related to cancer progression, including in nasopharyngeal carcinoma (NPC). However, the molecular mechanisms underlying miR-1 downregulation in NPC remain largely unknown, especially its association with Epstein-Barr virus (EBV). In this study we found that restoration of miR-1 dramatically inhibited cell invasion invitro, together with tumour growth and metastasis invivo. Importantly, we found that LMP1, an Epstein-Barr virus (EBV)-associated protein, suppressed miR-1 expression. Furthermore, we identified K-ras as a novel direct target of miR-1. Our results demonstrated for the first time that miR-1 was suppressed by LMP1 and its tumour-suppressive effects were mediated chiefly by repressing K-ras expression. We propose that miR-1 could serve as an independent biomarker to identify patients with different clinical characteristics.
引用
收藏
页码:427 / 432
页数:6
相关论文
共 23 条
[1]   Oncogenic K-Ras and Loss of Smad4 Mediate Invasion by Activating an EGFR/NF-κB Axis That Induces Expression of MMP9 and uPA in Human Pancreas Progenitor Cells [J].
Bera, Alakesh ;
Zhao, Shujie ;
Cao, Lin ;
Chiao, Paul J. ;
Freeman, James W. .
PLOS ONE, 2013, 8 (12)
[2]   EGF Receptor Promotes Prostate Cancer Bone Metastasis by Downregulating miR-1 and Activating TWIST1 [J].
Chang, Yung-Sheng ;
Chen, Wei-Yu ;
Yin, Juan Juan ;
Sheppard-Tillman, Heather ;
Huang, Jiaoti ;
Liu, Yen-Nien .
CANCER RESEARCH, 2015, 75 (15) :3077-3086
[3]   Syncope due to nasopharyngeal carcinoma [J].
Chen-Scarabelli, C ;
Kaza, AR ;
Scarabelli, T .
LANCET ONCOLOGY, 2005, 6 (05) :347-349
[4]   RETRACTED: Methylation mediated silencing of microRNA-1 gene and its role in hepatocellular carcinogenesis (Retracted Article) [J].
Datta, Jharna ;
Kutay, Huban ;
Nasser, Mohd W. ;
Nuovo, Gerard J. ;
Wang, Bo ;
Majumder, Sarmila ;
Liu, Chang-Gong ;
Volinia, Stefano ;
Croce, Carlo M. ;
Schmittgen, Thomas D. ;
Ghoshal, Kalpana ;
Jacob, Samson T. .
CANCER RESEARCH, 2008, 68 (13) :5049-5058
[5]   miR-216b suppresses tumor growth and invasion by targeting KRAS in nasopharyngeal carcinoma [J].
Deng, Min ;
Tang, Hailin ;
Zhou, Yanhong ;
Zhou, Ming ;
Xiong, Wei ;
Zheng, Ying ;
Ye, Qiurong ;
Zeng, Xi ;
Liao, Qianjin ;
Guo, Xiaofang ;
Li, Xiaoling ;
Ma, Jian ;
Li, Guiyuan .
JOURNAL OF CELL SCIENCE, 2011, 124 (17) :2997-3005
[6]   Global identification of microRNA-target RNA pairs by parallel analysis of RNA ends [J].
German, Marcelo A. ;
Pillay, Manoj ;
Jeong, Dong-Hoon ;
Hetawal, Amit ;
Luo, Shujun ;
Janardhanan, Prakash ;
Kannan, Vimal ;
Rymarquis, Linda A. ;
Nobuta, Kan ;
German, Rana ;
De Paoli, Emanuele ;
Lu, Cheng ;
Schroth, Gary ;
Meyers, Blake C. ;
Green, Pamela J. .
NATURE BIOTECHNOLOGY, 2008, 26 (08) :941-946
[7]   Pharmacogenomics and targeted therapy of cancer: Focusing on non-small cell lung cancer [J].
Haghgoo, Seyyed Mortaza ;
Allameh, Abdolamir ;
Mortaz, Esmaeil ;
Garssen, Johan ;
Folkerts, Gert ;
Barnes, Peter J. ;
Adcock, Ian M. .
EUROPEAN JOURNAL OF PHARMACOLOGY, 2015, 754 :88-97
[8]   The Epstein-Barr Virus-Encoded MicroRNA MiR-BART9 Promotes Tumor Metastasis by Targeting E-Cadherin in Nasopharyngeal Carcinoma [J].
Hsu, Chung-Yuan ;
Yi, Yung-Hsiang ;
Chang, Kai-Ping ;
Chang, Yu-Sun ;
Chen, Shu-Jen ;
Chen, Hua-Chien .
PLOS PATHOGENS, 2014, 10 (02)
[9]   Clinical Relevance of KRAS in Human Cancers [J].
Jancik, Sylwia ;
Drabek, Jiri ;
Radzioch, Danuta ;
Hajduch, Marian .
JOURNAL OF BIOMEDICINE AND BIOTECHNOLOGY, 2010,
[10]   Codelivery of Small Molecule Hedgehog Inhibitor and miRNA for Treating Pancreatic Cancer [J].
Kumar, Virender ;
Mondal, Goutam ;
Slavik, Paige ;
Rachagani, Satyanarayna ;
Batra, Surinder K. ;
Mahato, Ram I. .
MOLECULAR PHARMACEUTICS, 2015, 12 (04) :1289-1298