RRC ID 6820
Author Shinozaki A, Sakatani T, Ushiku T, Hino R, Isogai M, Ishikawa S, Uozaki H, Takada K, Fukayama M.
Title Downregulation of microRNA-200 in EBV-associated gastric carcinoma.
Journal Cancer Res
Abstract EBV-associated gastric carcinoma is a distinct gastric carcinoma subtype with characteristic morphologic features similar to those of cells that undergo epithelial-to-mesenchymal transition. The effect of microRNA abnormalities in carcinogenesis was investigated by measuring the expression of the epithelial-to-mesenchymal transition-related microRNAs, miR-200a and miR-200b, in 36 surgically resected gastric carcinomas using quantitative reverse transcription-PCR analysis. MiR-200 family expression was decreased in EBV-associated gastric carcinoma, as compared with that in EBV-negative carcinoma. Downregulation of the miR-200 family was found in gastric carcinoma cell lines infected with recombinant EBV (MKN74-EBV, MKN7-EBV, and NUGC3-EBV), accompanied by the loss of cell adhesion, reduction of E-cadherin expression, and upregulation of ZEB1 and ZEB2. E-cadherin expression was partially restored by transfection of EBV-infected cells with miR-200 family precursors. Reverse transcription-PCR analysis of primary precursors of miR-200 (pri-miR-200) revealed that the transcription of pri-miR-200 was decreased in EBV-infected cells. Transfection of MKN74 cells with BARF0, EBNA1, and LMP2A resulted in a decrease of pri-miR-200, whereas transfection with EBV-encoded small RNA (EBER) did not. These four latent genes contributed to the downregulation of the mature miR-200 family and the subsequent upregulation of ZEB1/ZEB2, resulting in the reduction of E-cadherin expression. These findings indicate that all the latency type I genes have a synergetic effect on the downregulation of the miR-200 family that leads to reduced E-cadherin expression, which is a crucial step in the carcinogenesis of EBV-associated gastric carcinoma.
Volume 70(11)
Pages 4719-27
Published 2010-6-1
DOI 10.1158/0008-5472.CAN-09-4620
PII 0008-5472.CAN-09-4620
PMID 20484038
MeSH Cadherins / biosynthesis Cadherins / genetics Cell Line, Tumor Down-Regulation Epstein-Barr Virus Infections / genetics* Epstein-Barr Virus Infections / metabolism Epstein-Barr Virus Infections / pathology* Gene Expression Regulation, Neoplastic Gene Expression Regulation, Viral Herpesvirus 4, Human / genetics Herpesvirus 4, Human / metabolism Herpesvirus 4, Human / physiology* Humans MicroRNAs / biosynthesis MicroRNAs / genetics* Reverse Transcriptase Polymerase Chain Reaction Stomach Neoplasms / genetics* Stomach Neoplasms / metabolism Stomach Neoplasms / pathology Stomach Neoplasms / virology* Transfection Virus Latency
IF 9.727
Times Cited 95
Human and Animal Cells MKN7(RCB0999) MKN74(RCB1002)