Epstein–Barr virus-encoded microRNA BART22 serves as novel biomarkers and drives malignant transformation of nasopharyngeal carcinoma

• Published in: Cell death & disease Vol. 13; no. 7; pp. 664 - 14
• Main Authors: Zhang, Ting, Chen, Zui, Deng, Jing, Xu, Kaixiong, Che, Di, Lin, Jiamin, Jiang, Ping, Gu, Xiaoqiong, Xu, Banglao
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 30.07.2022; Springer Nature B.V; Nature Publishing Group
• Subjects: 13/1; 13/105; 13/51; 14/32; 3' Untranslated Regions; 38/109; 38/91; 42/35; 631/67/1536/1665; 631/67/1858; 64/60; 82/16; Antibodies; Biochemistry; Biomarkers; Biomarkers - metabolism; Biomedical and Life Sciences; Cell Biology; Cell Culture; Epstein-Barr virus; Epstein-Barr Virus Infections; Herpesvirus 4, Human - genetics; Herpesvirus 4, Human - metabolism; Humans; Immunology; Life Sciences; Malignancy; Medical prognosis; Mesenchyme; Metastases; Metastasis; MicroRNAs; MicroRNAs - genetics; MicroRNAs - metabolism; miRNA; Molecular modelling; Nasopharyngeal carcinoma; Nasopharyngeal Carcinoma - pathology; Nasopharyngeal Neoplasms - genetics; Nasopharyngeal Neoplasms - pathology; Nomograms; RNA, Viral - genetics; Signal transduction; Throat cancer; Tumors; Wnt protein; β-Catenin
• ISSN: 2041-4889; 2041-4889
• DOI: 10.1038/s41419-022-05107-x

Nasopharyngeal carcinoma (NPC) is an epithelial malignancy ubiquitously associated with Epstein–Barr virus (EBV). EBV generates various viral microRNAs (miRNAs) by processing the BHRF1 and BamHI A rightward (BART) transcripts. These BART miRNAs are abundantly expressed in NPC, but their functions and molecular mechanisms remain largely unknown. Our study found that the EBV-encoded microRNA BART-22 was significantly upregulated in NPC tissues and positively correlated with tumor progression. Furthermore, we found that EBV-miR-BART-22 was a significant predictor of poor prognosis in NPC. A reliable nomogram model to predict the preoperative overall survival (OS) of NPC patients was established. The area under the receiver operating characteristic (ROC) curve value for 5-year survival was 0.91. Elevated levels of EBV-miR-BART-22 significantly promoted the epithelial-mesenchymal transition (EMT) and metastasis of NPC cells in vivo and in vitro. We found that EBV-miR-BART-22 directly targets the 3′-UTR of MOSPD2 mRNA to promote the EMT and metastasis of NPC cells by activating the Wnt/β-catenin signaling pathway. Our findings provide a potential prognostic biomarker and new insight into the molecular mechanisms of NPC metastasis.