| RRC ID |
67891
|
| 著者 |
Abe H, Kunita A, Otake Y, Kanda T, Kaneda A, Ushiku T, Fukayama M.
|
| タイトル |
Virus-host interactions in carcinogenesis of Epstein-Barr virus-associated gastric carcinoma: Potential roles of lost ARID1A expression in its early stage.
|
| ジャーナル |
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.
|
| 巻・号 |
16(9)
|
| ページ |
e0256440
|
| 公開日 |
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
|
| リソース情報 |
| ヒト・動物細胞 |
MKN74(RCB1002) |
