Oncotarget

Research Papers:

EBV-miR-BART10-3p facilitates epithelial-mesenchymal transition and promotes metastasis of nasopharyngeal carcinoma by targeting BTRC

Qijia Yan, Zhaoyang Zeng, Zhaojian Gong, Wenling Zhang, Xiayu Li, Baoyu He, Yali Song, Qiao Li, Yong Zeng, Qianjin Liao, Pan Chen, Lei Shi, Songqing Fan, Bo Xiang, Jian Ma, Ming Zhou, Xiaoling Li, Jianbo Yang, Wei Xiong and Guiyuan Li _

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Oncotarget. 2015; 6:41766-41782. https://doi.org/10.18632/oncotarget.6155

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Abstract

Qijia Yan1,2,3, Zhaoyang Zeng1,2,3, Zhaojian Gong2,4, Wenling Zhang2, Xiayu Li3, Baoyu He2, Yali Song2, Qiao Li2, Yong Zeng1, Qianjin Liao1, Pan Chen1, Lei Shi4, Songqing Fan4, Bo Xiang1,2,3, Jian Ma1,2,3, Ming Zhou1,2,3, Xiaoling Li1,2,3, Jianbo Yang1,5, Wei Xiong1,2,3 and Guiyuan Li1,2,3

1 Hunan Key Laboratory of Translational Radiation Oncology, Hunan Cancer Hospital and The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan, China

2 The Key Laboratory of Carcinogenesis of the Chinese Ministry of Health and The Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Cancer Research Institute, Central South University, Changsha, Hunan, China

3 Hunan Key Laboratory of Nonresolving Inflammation and Cancer, Disease Genome Research Center, The Third Xiangya Hospital, Central South University, Changsha, Hunan, China

4 The Second Xiangya Hospital, Central South University, Changsha, Hunan, China

5 Department of Laboratory Medicine and Pathology and Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota, United States of America

Correspondence to:

Zhaoyang Zeng, email:

Guiyuan Li, email:

Keywords: Epstein-Barr virus (EBV), nasopharyngeal carcinoma (NPC), EBV-miR-BART10-3p, BTRC, epithelial-mesenchymal transition (EMT)

Received: May 07, 2015 Accepted: September 30, 2015 Published: October 19, 2015

Abstract

Epstein-Barr virus (EBV) infection is closely associated with tumorigenesis and development of nasopharyngeal carcinoma (NPC), but the underlying molecular mechanisms remain poorly understood. It has been recently reported that EBV encodes 44 mature miRNAs, some of which were found to promote tumor development by targeting virus-infected host genes or self-viral genes. However, few targets of EBV encoded-miRNAs that are related to NPC development have been identified to date. In this study, we revealed that in NPC cells, EBV-miR-BART10-3p directly targets BTRC gene that encodes βTrCP (beta-transducin repeat containing E3 ubiquitin protein ligase). We found that EBV-miR-BART10-3p expression in clinical samples from a cohort of 106 NPC patients negatively correlated with BTRC expression levels. Over-expression of EBV-miR-BART10-3p and down-regulation of BTRC were associated with poor prognosis in NPC patients. EBV-miR-BART10-3p promoted the invasion and migration cabilities of NPC cells through the targeting of BTRC and regulation of the expression of the downstream substrates β-catenin and Snail. As a result, EBV-miR-BART10-3p facilitated epithelial-mesenchymal transition of NPC. Our study presents an unreported mechanism underlying EBV infection in NPC carcinogenesis, and provides a potential novel biomarker for NPC diagnosis, treatment and prognosis.


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