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miR-HCC2 suppresses hepatitis B virus replication by inhibiting the activity of the enhancer I/X promoter

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Abstract

miR-HCC2 has been reported to markedly promote the growth, metastasis, and stemness of hepatocellular carcinoma (HCC) cells in vitro and in vivo. Deep sequencing showed that miR-HCC2 was significantly upregulated in hepatitis B virus (HBV)-positive (HBV+) HCC tissue samples compared with HBV-negative (HBV-) HCC tissue samples. miR-HCC2 expression was further evaluated in HCC tissues and cells, and the expression of miR-HCC2 was found to be significantly higher in HBV+ HCC tissues and cells than in HBV- HCC tissues and cells, suggesting that high miR-HCC2 expression could be induced by HBV infection. To explore the relationship between miR-HCC2 and HBV, we investigated the effect of miR-HCC2 on HBV antigen expression, transcription, and replication. We found that miR-HCC2 was involved in the negative feedback regulation of HBV replication. Further mechanistic studies revealed that miR-HCC2 suppressed HBV replication by inhibiting the activity of the enhancer I/X promoter. Our study demonstrates the effect of the inhibition of miR-HCC2 on HBV gene expression and replication, which can help to illustrate the complex regulatory network involving host miRNAs and HBV.

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Data availability

The datasets used and/or analysed are available from the corresponding author on reasonable request.

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Acknowledgements

This work was supported by the National Natural Science Foundation of China (nos. 81602410 and 81773002) and the Natural Science Foundation of Tianjin (17JCQNJC11300).

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Authors and Affiliations

  1. Department of Pathogen Biology, School of Basic Medical Sciences, Tianjin Medical University, No. 22 Qi-Xiang-Tai Road, Tianjin, 300070, China

    Huijie Gao, Hongxia Fan & Hong Xie

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  1. Huijie Gao
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  2. Hongxia Fan
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  3. Hong Xie
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Contributions

GHJ contributed to the study conception and design. Material preparation, data collection, and analysis were performed by all authors. The draft of the manuscript was written by GHJ and XH. All authors reviewed the manuscript.

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Correspondence to Huijie Gao or Hong Xie.

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Ethical approval for this work was granted by the Ethics Committee of Tianjin Medical University.

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Gao, H., Fan, H. & Xie, H. miR-HCC2 suppresses hepatitis B virus replication by inhibiting the activity of the enhancer I/X promoter. Arch Virol 168, 282 (2023). https://doi.org/10.1007/s00705-023-05899-z

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