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

Cell Death Dis. 2022 Jul 30;13(7):664. doi: 10.1038/s41419-022-05107-x.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3' Untranslated Regions
  • Biomarkers / metabolism
  • Epstein-Barr Virus Infections*
  • Herpesvirus 4, Human / genetics
  • Herpesvirus 4, Human / metabolism
  • Humans
  • MicroRNAs* / genetics
  • MicroRNAs* / metabolism
  • Nasopharyngeal Carcinoma / pathology
  • Nasopharyngeal Neoplasms* / genetics
  • Nasopharyngeal Neoplasms* / pathology
  • RNA, Viral / genetics

Substances

  • 3' Untranslated Regions
  • Biomarkers
  • MicroRNAs
  • RNA, Viral