Abstract LB-469: An Epstein-Barr virus-encoded microRNA miR-BART5 upregulates human cellular microRNA miR-146a and downregulates IRAK1/NFκB in stomach cancer cells

Abstract

Abstract Epstein-Barr virus (EBV) contributes to the development of the specific subsets of stomach cancer, nasopharyngeal cancer and malignant lymphoma etc. MicroRNAs (miRNAs) have been implicated in the regulation of various pathobiological processes in cancer. Recently, EBV-encoded viral miRNAs have been disclosed, whereas the functions of which remain largely unknown. A notable example of this is the human miRNA, which is targeted by viral miRNA. In this study, we investigated EBV-encoded viral miRNA miR-BART5/human cellular target interaction. The EBV miR-BART5 in EBV-infected stomach cancer cell line SNU719 was highly expressed comparing with that in EBV-infected lymphoma cell lines, Raji and Jijoye. In addition, EBV-infected stomach cancer cell revealed high level of human cellular miR-146a comparing with EBV-negative stomach cancer cells SNU601 and SNU216. Either miR-BART5 inhibitor product (anti-miR-BART5) or miR-BART5 precursor product (pre-miR-BART5) was transfected into EBV-infected stomach cancer cell, or EBV-negative stomach cancer cell, respectively. As a result, the expression of human cellular miR-146a was decreased in EBV-infected stomach cancer cell transfected with anti-miR-BART5 comparing with that in its original cell, while miR-146a was increased in EBV-negative stomach cancer cell transfected with pre-miR-BART5. As a predicted target of miR-146a, based on predicted base pairing using miRBase online program, we focused on interleukin-1 receptor-associated kinase 1 (IRAK1). Once EBV-negative stomach cancer cell was transfected with pre-miR-BART5, IRAK1 protein level was reduced by 50%, and nuclear factor-kappaB (NF-κB) (p65) was decreased. To check miR-BART5 influences on cellular biologic properties, when pre-miR-BARF5 was transfected into EBV-negative stomach cancer cell, invasion capacity of cancer cell was suppressed with a statistical significance. In conclusion, miR-BART5 could inhibit invasion of stomach cancer cell, which is in part due to the upregulation of miR-146a and downregulation of IRAK-1/ NF-κB signal pathway, offering clinicopathologic entity with a better prognosis to EBV-infected stomach cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr LB-469. doi:1538-7445.AM2012-LB-469