RRC ID 67891
Author Abe H, Kunita A, Otake Y, Kanda T, Kaneda A, Ushiku T, Fukayama M.
Title Virus-host interactions in carcinogenesis of Epstein-Barr virus-associated gastric carcinoma: Potential roles of lost ARID1A expression in its early stage.
Journal PLoS One
Abstract Epstein-Barr virus (EBV)-associated gastric carcinoma (EBVaGC) is a distinct molecular subtype of gastric cancer characterized by viral infection and cellular abnormalities, including loss of AT-rich interaction domain 1A (ARID1A) expression (lost ARID1A). To evaluate the significance of lost ARID1A in the development of EBVaGC, we performed in situ hybridization of EBV-encoded RNA (EBER) and immunohistochemistry of ARID1A in the non-neoplastic gastric mucosa and intramucosal cancer tissue of EBVaGC with in vitro infection analysis of ARID1A-knockdown and -knockout gastric cells. Screening of EBER by in situ hybridization revealed a frequency of approximately 0.2% EBER-positive epithelial cells in non-neoplastic gastric mucosa tissue samples. Six small foci of EBV-infected epithelial cells showed two types of histology: degenerated (n = 3) and metaplastic (n = 3) epithelial cells. ARID1A was lost in the former type. In intramucosal EBVaGC, there were ARID1A-lost (n = 5) and -preserved tumors (n = 7), suggesting that ARID1A-lost carcinomas are derived from ARID1A-lost precursor cells in the non-neoplastic mucosa. Lost ARID1A was also observed in non-neoplastic mucosa adjacent to an ARID1A-lost EBVaGC. In vitro experiments using siRNA knockdown and the CRISPR/Cas9-knockout system demonstrated that transient reduction or permanent loss of ARID1A expression markedly increased the efficiency of EBV infection to stomach epithelial cells. Taken together, lost ARID1A plays a role in initiating EBV-driven carcinogenesis in stomach epithelial cells, which develop to a distinct subtype of EBVaGC within the proper mucosal layer. Lost ARID1A is one of the constituents of virus-host interactions in the carcinogenesis of EBVaGC.
Volume 16(9)
Pages e0256440
Published 2021-1-1
DOI 10.1371/journal.pone.0256440
PII PONE-D-21-04978
PMID 34469459
PMC PMC8409614
MeSH Adult Aged Carcinogenesis / genetics* Carcinogenesis / pathology Carcinoma / genetics* Carcinoma / pathology Carcinoma / virology Cell Line, Tumor DNA Methylation DNA-Binding Proteins / deficiency* DNA-Binding Proteins / genetics Epstein-Barr Virus Infections / genetics* Epstein-Barr Virus Infections / pathology Epstein-Barr Virus Infections / virology Female Gastric Mucosa / pathology Gastric Mucosa / virology Gene Expression Regulation, Neoplastic Gene Knockout Techniques Herpesvirus 4, Human / isolation & purification Herpesvirus 4, Human / pathogenicity Host-Pathogen Interactions / genetics Humans Male Middle Aged Stomach Neoplasms / genetics* Stomach Neoplasms / pathology Stomach Neoplasms / virology Transcription Factors / deficiency* Transcription Factors / genetics
IF 2.74
Human and Animal Cells MKN74(RCB1002)