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, Guiyuan Li

Research output: Contribution to journalArticlepeer-review

68 Scopus citations

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. Overexpression 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.

Original languageEnglish (US)
Pages (from-to)41766-41782
Number of pages17
JournalOncotarget
Volume6
Issue number39
DOIs
StatePublished - 2015

Keywords

  • BTRC
  • EBV-miR-BART10-3p
  • Epithelial-mesenchymal transition (EMT)
  • Epstein-Barr virus (EBV)
  • Nasopharyngeal carcinoma (NPC)

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