EBV-miR-BART12 inhibits cell migration and proliferation by targeting Snail expression in EBV-associated gastric cancer

Abstract

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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Acknowledgements

This work was supported by the National Natural Science Foundation of China [NSFC 81571995] and the Natural Science Foundation of Shandong Province [ZR2017BH106].

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Correspondence to Bing Luo.

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All procedures performed in this study involving human participants were in accordance with the ethical standards of the Medical Ethics Committee at the Medical College of Qingdao University and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.

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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

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