Comprehensive profiling of virus microRNAs of Epstein–Barr virus‐associated gastric carcinoma: highlighting the interactions of ebv‐Bart9 and host tumor cells. Issue 1 (January 2017)

• Record Type: Journal Article
• Authors: Tsai, Chun‐Yi; Liu, Yu Yin; Liu, Keng‐Hao; Hsu, Jun‐Te; Chen, Tse‐Ching; Chiu, Cheng‐Tang; Yeh, Ta‐Sen
• Is Part Of: Journal of gastroenterology and hepatology. Volume 32:Issue 1(2017)
• Page Start: 82
• Page End: 91
• Publication Date: 2017-01
• Subjects: EBV‐associated gastric cancer -- ebv‐microRNA -- gastric cancer: clinical research; Gastroenterology -- Periodicals; Digestive organs -- Diseases -- Periodicals; Liver -- Diseases -- Periodicals; Gastroenterology -- Periodicals; Liver Diseases -- Periodicals; 616.33
• DOI: 10.1111/jgh.13432
• Languages: English
• ISSNs: 0815-9319

Abstract

Abstract: Background and Aim: 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.