Epstein-Barr virus BARF1-induced NF?B/miR-146a/SMAD4 alterations in stomach cancer cells.

ABSTRACT: Epstein-Barr virus (EBV)-encoded BamHI-A rightward frame 1 (BARF1) is a putative viral oncogene in EBV-infected stomach cancer. The aim of the present study was to investigate BARF1-induced cellular protein and microRNA alterations. In this study, BARF1-expressing stomach cancer cells showed a high rate of proliferation, high levels of NF?B, and miR-146a upregulation, which was reversed by NF?B knockdown. During BARF1-induced NF?B upregulation, hCSF1 receptor level was unchanged. Knockdown of BARF1 in the naturally EBV-infected YCCEL1 stomach cancer cells suppressed cell proliferation, and downregulated NF?B and miR-146a. SMAD4 was identified as a miR-146a target and was downregulated in BARF1-expressing cells, whereas SMAD4 expression was restored by anti-miR-146a. Knockdown of BARF1 in YCCEL1 cells upregulated SMAD4, and this effect was reversed by miR-146a overexpression. Transfection of BARF1-expressing cells with pCEP4-SMAD4 abolished the cell proliferating effect of BARF1. In stomach cancer tissues, miR-146a was expressed at higher levels, and more frequent NF?B nuclear positivity immunohistochemically, but not of SMAD4 nuclear loss was found in the EBV-positive group compared with the EBV-negative group. In conclusion, EBV-encoded BARF1 promotes cell proliferation in stomach cancer by upregulating NF?B and miR-146a and downregulating SMAD4, thereby contributing to EBV-induced stomach cancer progression.

SUBMITTER: Kim DH 

PROVIDER: S-EPMC5347686 | biostudies-literature | 2016 Dec

REPOSITORIES: biostudies-literature