title: Profiling of Epstein-Barr virus-encoded microRNAs in nasopharyngeal carcinoma reveals potential biomarkers and oncomirs.
abstract: BACKGROUND
  Epstein-Barr virus (EBV) microRNAs are abundant in nasopharyngeal carcinoma (NPC) tumors. With recent advances in serum microRNA detection, the distinct presence of EBV microRNAs in serum could aid in screening endemic regions for NPC. A proposed network of genes targeted by these microRNAs could also shed light on EBV-associated tumorigenesis.
  
  
  METHODS
  MicroRNA microarray profiling of 5 paired NPC biopsies was followed by validation of 12 up-regulated EBV microRNAs (BART1-3p, 2-5p, 5, 6-5p, 6-3p, 7, 8, 9, 14, 17-5p, 18-5p, 19-3p) in 15 additional cases by real-time polymerase chain reaction. Tumor (cellular) and serum microRNA copy numbers from the same 15 patients were correlated. Expression of the same microRNAs were also examined in EBV-positive cell lines C666 and NP460hTERT+EBV. Bioinformatic tools helped predict cellular target genes, which were later confirmed by gene expression analysis.
  
  
  RESULTS
  The authors' high-throughput approach shows that EBV microRNAs are generally more up-regulated than microRNAs of human origin. Twenty-nine of 39 EBV microRNAs were significantly up-regulated in tumor versus their nontumor biopsies (P < .05). Upon successfully validating 12 selected EBV microRNAs in 15 additional paired NPC cases, the authors found that their distinct presence in the serum of NPC patients positively correlated with cellular copy numbers of EBV microRNAs. Further investigation of potential EBV microRNA target genes revealed inhibition of tumor suppressor genes (eg, PTEN) and extensive deregulation of several pathways frequently involved in NPC (eg, Wnt signaling).
  
  
  CONCLUSIONS
  Increasing knowledge of host-virus interaction via microRNAs may provide feasible explanations underlying NPC tumorigenesis along with the development of biomarkers for screening high-risk populations.
authors: Department of Clinical Oncology and Center for Cancer Research, University of Hong Kong, Pokfulam, Hong Kong.
authors: Alissa Michelle Go
authors: AM
authors: Wong
authors: Kar Lok
authors: KL
authors: Kong
authors: Janice Wing Hang
authors: JW
authors: Tsang
authors: Dora Lai Wan
authors: DL
authors: Kwong
authors: Xin-Yuan
authors: XY
authors: Guan
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics*; D015153:Blotting, Western; D016022:Case-Control Studies; D020031:Epstein-Barr Virus Infections / Q000097:blood / Q000235:genetics / Q000821:virology; D005260:Female; D020869:Gene Expression Profiling; D004854:Herpesvirus 4, Human / Q000235:genetics* / Q000302:isolation & purification; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000097:blood / Q000235:genetics*; D008875:Middle Aged; D009303:Nasopharyngeal Neoplasms / Q000097:blood / Q000235:genetics* / Q000821:virology; D020411:Oligonucleotide Array Sequence Analysis; D009857:Oncogenes; D011379:Prognosis; D012367:RNA, Viral / Q000097:blood / Q000235:genetics*; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D014408:Biomarkers, Tumor; D035683:MicroRNAs; D012367:RNA, Viral