Tumor Biology

, Volume 37, Issue 3, pp 3749–3756 | Cite as

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

  • Xiaokun Bian
  • Yuanquan Si
  • Min Zhang
  • Ran Wei
  • Xiaomin Yang
  • Hao Ren
  • Guixi Zheng
  • Chuanxin Wang
  • Yi Zhang
Research Article


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.


HLA-G HBV miR-152 Immune tolerance 



Hepatitis B virus


Chronic HBV infection


Hepatocellular carcinoma


Human leucocyte antigen-G


Natural killer cell


Dendritic cell


3′ Untranslated region


Hepatitis B surface antigen




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


Real-time polymerase chain reaction


Flow cytometric analysis


Cytotoxic T lymphocyte


Single nucleotide polymorphisms



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


Supplementary material

13277_2015_3669_MOESM1_ESM.docx (17 kb)
ESM 1 (DOCX 17 kb)


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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2015

Authors and Affiliations

  • Xiaokun Bian
    • 1
    • 2
  • Yuanquan Si
    • 1
    • 3
  • Min Zhang
    • 4
  • Ran Wei
    • 1
  • Xiaomin Yang
    • 1
  • Hao Ren
    • 1
  • Guixi Zheng
    • 1
  • Chuanxin Wang
    • 1
  • Yi Zhang
    • 1
  1. 1.Department of Clinical LaboratoryQilu Hospital of Shandong UniversityJinanChina
  2. 2.Department of Clinical LaboratoryWeifang People’s HospitalShandongChina
  3. 3.Department of Clinical LaboratoryProvincial Hospital Affiliated to Shandong UniversityJinanChina
  4. 4.Department of MedicineShandong Provincial Chest HospitalJinanChina

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