Epstein-Barr virus-encoded miR-BART6-3p inhibits cancer cell metastasis and invasion by targeting long non-coding RNA LOC553103.

Baoyu He,Can Guo,Guiyuan Li,Weiming Li,Hao Bo,Yong Li,Yingfen Wu,Zhaojian Gong,Ming Zhou,Fang Wei,Xiaoling Li,Zhaoyang Zeng,Bo Xiang,Qianjin Liao,Yumin Wang,Pan Chen,Xiayu Li,Jian Ma,Xuyu Zu,Xiong Wang

doi:10.1038/cddis.2016.253

Abstract

Epstein-Barr virus (EBV) infection is causatively related to a variety of human cancers, including nasopharyngeal carcinoma (NPC) and gastric cancer (GC). EBV encodes 44 mature miRNAs, a number of which have been proven to promote carcinogenesis by targeting host genes or self-viral genes. However, in this study, we found that an EBV-encoded microRNA, termed EBV-miR-BART6-3p, inhibited EBV-associated cancer cell migration and invasion including NPC and GC by reversing the epithelial–mesenchymal transition (EMT) process. Using microarray analysis, we identified and validated that a novel long non-coding RNA (lncRNA) LOC553103 was downregulated by EBV-miR-BART6-3p, and LOC553103 knockdown by specific siRNAs phenocopied the effect of EBV-miR-BART6-3p, while LOC553103 overexpression promoted cancer cell migration and invasion to facilitate EMT. In conclusion, we determined that EBV-miR-BART6-3p, a microRNA encoded by oncogenic EBV, inhibited EBV-associated cancer cell migration and invasion by targeting and downregulating a novel lncRNA LOC553103. Thus, our study presents an unreported mechanism underlying EBV infection in EBV-associated cancer carcinogenesis, and provides a potential novel diagnosis and treatment biomarker for NPC and other EBV-related cancers.

Highlights

Epstein-Barr virus (EBV) is a gamma herpesvirus, which infects more than 90% of the world’s adult population.[1]
We previously established a comprehensive EBV-miRNA profiles in nasopharyngeal carcinoma (NPC) and found that 40 EBV miRNAs from the BamHI A rightward transcript (BART) transcript were highly expressed in NPC.[23]
Because pseudopods and filopodia are essential for cell migration, we investigated in detail whether EBV-miRBART6-3p affected cancer cell metastasis and invasion in this study

Summary

Introduction

Epstein-Barr virus (EBV) is a gamma herpesvirus, which infects more than 90% of the world’s adult population.[1]. It has become apparent that EBV encodes for a large number of microRNAs (miRNAs), including BART cluster and BHRF cluster.[13,14] The largest set of miRNAs is the BamHI A rightward transcript (BART) miRNAs, which is composed of 40 miRNAs expressed in all forms of EBV latency.[13] They were reported to promote viral latency or cancer development by targeting both viral and cellular genes.[15,16,17,18,19,20,21,22]. Unlike the majority of the BART cluster miRNAs, we found that EBV-miR-BART6-3p reversed the epithelial–mesenchymal transition (EMT) phenotype, and inhibited cancer cell migration and invasion.

Methods

Results

Conclusion