Epstein-Barr virus (EBV) was the first oncovirus found to encode microRNAs. In EBV-associated gastric cancer (EBVaGC), EBV-encoded BamHI-A rightward transcript microRNAs (BARTs) are highly expressed. However, the role of BARTs in EBVaGC remains obscure. In this study, we found that EBV-miR-BART12 (miR-BART12) inhibits cell proliferation and migration. Zinc finger protein SNAI1 (Snail) is an important epithelial-mesenchymal transition (EMT) inducer, and overexpression of Snail is closely associated with cancer metastasis. Here, we report that Snail expression in EBVaGC cells is lower than in EBV-negative gastric cancer (EBVnGC) cells. A dual luciferase reporter assay showed that miR-BART12 targets Snail directly by interacting with its 3ʹ-UTR. A CHX chase assay revealed that miR-BART12 accelerates the degradation of Snail. Furthermore, we found that miR-BART12 can regulate the expression of EMT-related genes. Flow cytometry analysis showed that transfection with miR-BART12 induced G2/M phase arrest and promoted cell apoptosis. In summary, the results of our study have suggested a new mechanism by which BARTs can repress cell proliferation and migration in gastric cancer.
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This work was supported by the National Natural Science Foundation of China [NSFC 81571995] and the Natural Science Foundation of Shandong Province [ZR2017BH106].
The authors declare that they have no competing interests.
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Li, J., Zhang, Y., Liu, J. et al. EBV-miR-BART12 inhibits cell migration and proliferation by targeting Snail expression in EBV-associated gastric cancer. Arch Virol 166, 1313–1323 (2021). https://doi.org/10.1007/s00705-021-05001-5