title: Comprehensive profiling of virus microRNAs of Epstein-Barr virus-associated gastric carcinoma: highlighting the interactions of ebv-Bart9 and host tumor cells.
abstract: OBJECTIVE
  Epstein-Barr virus (EBV) is suggested to actively utilize its ebv-microRNAs (miRNAs) to manipulate viral and cellular functions during neoplasia transformation. A systemic profiling of ebv-miRNAs expressed in EBV-associated gastric carcinoma (EBVa GC) helps understand its epigenetic regulation of carcinogenesis.
  
  
  METHODS
  A total of 1039 patients with gastric cancer were screened for EBVa GC using EBV-encoded RNAs in situ hybridization. A comprehensive profiling of ebv-miRNAs expressed in EBVa GC was constructed using stem-loop quantitative polymerase chain reaction. Functional assay of specific ebv-miRNA was conducted. Expression of epithelial-to-mesenchymal transition (EMT) markers among EBVa GC and non-EBVa GC was compared.
  
  
  RESULTS
  The prevalence of EBVa GC was 5.0% (52 out of 1039) in our series. The most abundant ebv-miRNAs of EBVa GC were Bart4, followed by Bart11, Bart2, Bart6, Bart9, and Bart18, in the decreasing order. Of them, Bart9 exhibited the same seed sequence as to hsa miR-200a and miR-141. Expression of E-cadherin of EBV-positive SNU-719 was increased after BART9 knockdown. Depleting endogenous Bart9 of SNU-719 induced a surged expression of miR-200a and miR-141, accompanied by decreased proliferative and invasive ability. Expression of mesenchymal markers in EBVa GC was increased compared with those of non-EBVa GC, albeit the two cohorts exhibited a comparable long-term survival.
  
  
  CONCLUSIONS
  We constructed a comprehensive profiling of ebv-miRNAs in EBVa GC. BART9 plays an important role during carcinogenesis through EMT. Inherent mesenchymal phenotype of EBVa GC represents a unique virus-induced morphology and microenvironment rather than being able to predict the prognosis.
authors.affiliation: Department of Surgery, Chang Gung Memorial Hospital at Linkou, Chang Gung University College of Medicine, Taoyuan, Taiwan.
authors.forename: Chun-Yi
authors.initials: CY
authors.lastname: Tsai
authors.affiliation: Department of Surgery, Chang Gung Memorial Hospital at Linkou, Chang Gung University College of Medicine, Taoyuan, Taiwan.
authors.forename: Yu Yin
authors.initials: YY
authors.lastname: Liu
authors.affiliation: Department of Surgery, Chang Gung Memorial Hospital at Linkou, Chang Gung University College of Medicine, Taoyuan, Taiwan.
authors.forename: Keng-Hao
authors.initials: KH
authors.lastname: Liu
authors.affiliation: Department of Surgery, Chang Gung Memorial Hospital at Linkou, Chang Gung University College of Medicine, Taoyuan, Taiwan.
authors.forename: Jun-Te
authors.initials: JT
authors.lastname: Hsu
authors.affiliation: Department of Pathology, Chang Gung Memorial Hospital at Linkou, Chang Gung University College of Medicine, Taoyuan, Taiwan.
authors.forename: Tse-Ching
authors.initials: TC
authors.lastname: Chen
authors.affiliation: Department of Gastroenterology, Chang Gung Memorial Hospital at Linkou, Chang Gung University College of Medicine, Taoyuan, Taiwan.
authors.forename: Cheng-Tang
authors.initials: CT
authors.lastname: Chiu
authors.affiliation: Department of Surgery, Chang Gung Memorial Hospital at Linkou, Chang Gung University College of Medicine, Taoyuan, Taiwan.
authors.forename: Ta-Sen
authors.initials: TS
authors.lastname: Yeh
mesh_terms: D000368:Aged; D044127:Epigenesis, Genetic / Q000235:genetics*; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics*; D005260:Female; D015870:Gene Expression; D004854:Herpesvirus 4, Human / Q000235:genetics*; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000502:physiology; D008875:Middle Aged; D012367:RNA, Viral / Q000502:physiology; D013274:Stomach Neoplasms / Q000473:pathology* / Q000821:virology*
chemical_list: D035683:MicroRNAs; D012367:RNA, Viral
keywords: EBV-associated gastric cancer; ebv-microRNA; gastric cancer: clinical research