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Down-expression of miR-152 lead to impaired anti-tumor effect of NK via upregulation of HLA-G

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Tumor Biology

Abstract

It is known that chronic HBV infection (CHB) is the major risk factor for hepatocellular carcinoma (HCC) because CHB could not only cause liver tumorigenesis but also lead to change of local microenviroment and lower immune response to infected and cancerous cells (immune tolerance). Human leucocyte antigen-G (HLA-G) belongs to a non-classic MHC-I family and was considered to be an immune tolerance molecule, which could bind to immunosuppressive receptors of natural killer cell (NK) and T cells and trigger immunosuppressive signaling. Recently, numerous studies highlighted that microRNAs (miRNAs) were significantly differentially expressed in HCC tumorigenesis, and the expression was tissue-specific, indicating that miRNAs may cause great epigenetic changes in HCC tumorigenesis. In this study, we found that the expression of HLA-G was upregulated by hepatitis B virus (HBV) infection and miR-152; a HLA-G-targeting miRNA was downregulated by HBV infection. And high expression of HLA-G further suppressed NK against cancer cells, providing a new concept that miR-152 was involved in HBV-induced hepatocellular carcinoma.

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Abbreviations

HBV:

Hepatitis B virus

CHB:

Chronic HBV infection

HCC:

Hepatocellular carcinoma

HLA-G:

Human leucocyte antigen-G

NK:

Natural killer cell

DC:

Dendritic cell

3′UTR:

3′ Untranslated region

HBsAg:

Hepatitis B surface antigen

IHC:

Immunohistochemical

MTT:

3-(4,5-Dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide

RT-PCR:

Real-time polymerase chain reaction

FACS:

Flow cytometric analysis

CTL:

Cytotoxic T lymphocyte

SNPs:

Single nucleotide polymorphisms

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Acknowledgments

We thank Prof. Zhang (Institute of Immunopharmacology and Immunotherapy, School of Pharmaceutical Sciences, Shandong University, China) for providing NKL cell lines and Dr. He (Health Science Center, University of Texas, San Antonio) for providing pSuper-HBV plasmid. This study was supported in part by grants from the Shandong Province Science Foundation for Key Programs (2008GG30002017 and 2010GSF10274), the University Innovation Program from Jinan, Shandong Province (201004050), and National Key Clinical Medical Specialties foundation.

Conflicts of interest

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Authors and Affiliations

  1. Department of Clinical Laboratory, Qilu Hospital of Shandong University, Jinan, China

    Xiaokun Bian, Yuanquan Si, Ran Wei, Xiaomin Yang, Hao Ren, Guixi Zheng, Chuanxin Wang & Yi Zhang

  2. Department of Clinical Laboratory, Weifang People’s Hospital, Shandong, China

    Xiaokun Bian

  3. Department of Clinical Laboratory, Provincial Hospital Affiliated to Shandong University, Jinan, China

    Yuanquan Si

  4. Department of Medicine, Shandong Provincial Chest Hospital, Jinan, China

    Min Zhang

Authors
  1. Xiaokun Bian
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  2. Yuanquan Si
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  3. Min Zhang
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  4. Ran Wei
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  5. Xiaomin Yang
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  6. Hao Ren
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  7. Guixi Zheng
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  8. Chuanxin Wang
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  9. Yi Zhang
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Corresponding author

Correspondence to Yi Zhang.

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Bian, X., Si, Y., Zhang, M. et al. Down-expression of miR-152 lead to impaired anti-tumor effect of NK via upregulation of HLA-G. Tumor Biol. 37, 3749–3756 (2016). https://doi.org/10.1007/s13277-015-3669-7

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  • DOI: https://doi.org/10.1007/s13277-015-3669-7

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