Abstract 1400: An additive effect of ebv-miR-BART5-5p and hsa-miR18a-5p in the downregulation of CDH1 transcript in Epstein-Barr virus associated gastric cancer

Abstract

Background. Nine percent of Gastric Cancer (GC) is associated with Epstein-Barr virus (EBV-associated GC), with significant variations in the global prevalence rates. Emerging evidence shows that, in addition to cellular miRNAs, viral miRNAs can also bind human mRNAs. EBV miRNAs are examples of this binding and are associated with oncogenic capacities of EBV. ebv-miR-BART5-5p shares the exact seed sequence with hsa-miR-18a-5p. However, common mRNA targets have not been fully described. The aim of this study is to determine predicted targets shared by both miRNAs in EBV-associated GC. Methodology. By in house method we identified predicted mRNA targets for ebv-miR-BART5-5p and hsa-miR-18a-5p. These targets were queried in published results from the supplementary files of the STAD TCGA study and miRwalk 2.0 software. Validation was performed in 7 EBV-associated GC (cases) and 6 EBV-negative GC (controls) samples by miQ-PCR (ebv-miR-BART5-5p and hsa-miR-18a-5p) and qRT-PCR (predicted targets). Results. We identified 25 downregulated and 11 upregulated mRNAs in EBV-associated GC cases compared with EBV-negative tumors in validated databases. Interestingly CDH1, which has been associated with diffuse and hereditary GC, was among the predicted targets by miRwalk 2.0. In clinical samples of EBV-associated GC, ebv-miR-BART5-5p and hsa-miR-18a-5p were overexpressed compared with control samples (p=0.0253 and p=0.0205, respectively). Furthermore, CDH1 was downregulated in EBV-associated tumors (p=0.0290). Conclusion: We identified a common human mRNA target, the CDH1 transcript for ebv-miR-BART5-5p and hsa-miR-18a-5p in EBV-associated GC. An additive effect can be suggested between both miRNAs, which may explain the unique downregulation of CDH1 in EBV-associated GC. This work warrants future validation in vitro, as well as in a larger cohort of EBV-associated GC. Grant support: CONICYT-FONDAP-15130011, Fondecyt Regular-1191928 and Fondecyt PostDoc-3201028 Citation Format: Keila Torres, Natalia Landeros, Ignacio Wichmann, Allan Peñaloza-Otárola, Iva Polakovicova, Vinicius Maracaja-Coutinho, Maria Jose Maturana, Franz Villaroel-Espindola, Alejandro Corvalan. An additive effect of ebv-miR-BART5-5p and hsa-miR18a-5p in the downregulation of CDH1 transcript in Epstein-Barr virus associated gastric cancer [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 1400.