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MiR-BART1-3p and BART18-5p inhibit cell migration, proliferation and activate autophagy in Epstein-Barr virus-associated gastric cancer by targeting erythropoietin-producing human hepatocellular 2

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Abstract

Epstein-Barr virus (EBV) is a human tumor-associated virus that encodes various microRNAs. EBV infection causes a variety of malignant tumors, including nasopharyngeal carcinoma and gastric cancer, etc. EBV-associated gastric cancer (EBVaGC) has unique molecular characteristics from other gastric cancers, but its pathogenic mechanism remains unclear. In recent years, erythropoietin-producing human hepatocellular 2 (EphA2) has been reported to be highly expressed in various cancers and promote tumor growth and metastasis. As an important cancer oncogene, EphA2 is a potential therapeutic target. However, whether EBV is involved in the regulation of EphA2 and thus affects the progression of EBVaGC remains unclear. In this study, we found that the expression of EphA2 in EBVaGC cells was significantly lower than that in EBV-negative gastric cancer (EBVnGC) cells. Additionally, overexpression of EphA2 in EBVaGC cells promoted migration and proliferation, and inhibited autophagy. EBV-miR-BART1-3p and BART18-5p were found to target the 3’-UTR of EphA2 and down-regulate its expression. Our results suggest that EBV may be involved in gastric cancer progression by targeting EphA2 through BART1-3p and BART18-5p.

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Data availability

The datasets analysed during the current study are referenced in the text and publicly available.

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Acknowledgements

This work was supported by Natural Science Foundation of Shandong Province [ZR2020MH302; ZR2020MC020]; Qingdao Science and Technology Benefit the People Demonstration and Guidance Special Project (20-3-4-35-nsh).

Funding

Natural Science Foundation of Shandong Province, ZR2020MC020,ZR2020MH302, Qingdao Science and Technology Benefit the People Demonstration and Guidance Special Project, 20-3-4-35-nsh

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Authors and Affiliations

  1. Department of Pathogenic Biology, School of Basic Medicine, Qingdao University, 308 Ningxia Road, Qingdao, 266021, People’s Republic of China

    Duo Shi, Wen Liu, Xing Zhang, Yan Zhang & Bing Luo

  2. Department of Clinical Laboratory, Zibo Central Hospital, ZiBo, 255036, China

    Yan Zhang

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Bing Luo and Duo Shi conceived the experiments; Duo Shi performed the experiments; Wen Liu and Xing Zhang analyzed the experimental data; Duo Shi and Yan Zhang revised the manuscript. All authors reviewed and approved the final manuscript.

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Correspondence to Yan Zhang or Bing Luo.

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Shi, D., Liu, W., Zhang, X. et al. MiR-BART1-3p and BART18-5p inhibit cell migration, proliferation and activate autophagy in Epstein-Barr virus-associated gastric cancer by targeting erythropoietin-producing human hepatocellular 2. Virus Genes 59, 703–715 (2023). https://doi.org/10.1007/s11262-023-02023-w

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