Gold nano-particles (AuNPs) carrying anti-EBV-miR-BART7-3p inhibit growth of EBV-positive nasopharyngeal carcinoma.

Longmei Cai,Yuxiang Chen,Jinkun Liu,Hongbing Cai,Yaoyong Lu,Jianguo Wang,Xiaona Zhang,Ying Wang,Xin Li,Xiaoming Lyu,Jinbang Li

doi:10.18632/oncotarget.3046

Abstract

Epstein-Barr virus (EBV) infection is a major etiological factor for nasopharyngeal carcinoma (NPC). Several EBV-encoded BART miRNAs have been associated with viral latency, immune escape, cell survival, cell proliferation and apoptosis. Here, we report that EBV-miR-BART7-3p, an EBV-encoded BART miRNA highly expressed in NPC, was correlated with cell-cycle progression in vitro and increased tumor formation in vivo. This viral miRNA stimulated the PTEN/PI3K/Akt pathway and induced c-Myc and c-Jun. Knockdown of PTEN mimicked EBV-miR-BART7-3p-induced tumorigenic phenotype. Based on these results, we conducted a therapeutic experiment by using gold nano-particles (AuNPs) carrying anti-EBV-miR-BART7-3p. Silencing of EBV-miR-BART7-3p reduced tumor growth in animal model. We conclude that EBV-miR-BART7-3p favors carcinogenesis, representing a potential target for miRNA-based therapy.

Highlights

Nasopharyngeal carcinoma (NPC) is a malignancy derived from nasopharyngeal epithelium and is highly prevalent in Southern China and Southeast Asia
We report that Epstein-Barr virus (EBV)-miR-BART7-3p, an EBV-encoded BART miRNA highly expressed in nasopharyngeal carcinoma (NPC), was correlated with cell-cycle progression in vitro and increased tumor formation in vivo
We have recently discovered that highly expressed EBV-miR-BART7-3p was closely associated with NPC metastasis and EMT [24]

Summary

Introduction

Nasopharyngeal carcinoma (NPC) is a malignancy derived from nasopharyngeal epithelium and is highly prevalent in Southern China and Southeast Asia. Radiotherapy can effectively control early stage NPC, the average 5-year survival rate after therapy is less than 30–40% in the patients with advanced NPC [1]. Due to no obvious symptoms at early stage, more than 60% of clinical NPC patients are overlooked and reach advanced stages [2, 3]. It is necessary to discover novel therapeutic targets and interventions for effectively treating NPC. MicroRNAs (miRNAs) are endogenous non-coding RNAs that suppress gene expression post-transcriptionally by targeting the 3’UTRs of specific mRNAs. MicroRNAs (miRNAs) are endogenous non-coding RNAs that suppress gene expression post-transcriptionally by targeting the 3’UTRs of specific mRNAs They have emerged as important regulators of physiology and disease, and presented the important therapeutic potential

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Conclusion