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Liu W, Zheng X, Wang J, et al. MicroRNA-138 Regulates T-Cell Function by Targeting PD-1 in Patients with Hepatitis B Virus-Related Liver Diseases. Lab Med. 2021;52(5):439-451doi: 10.1093/labmed/lmaa110.
Liu, W., Zheng, X., Wang, J., He, Q., Li, J., Zhang, Z., & Liu, H. (2021). MicroRNA-138 Regulates T-Cell Function by Targeting PD-1 in Patients with Hepatitis B Virus-Related Liver Diseases. Laboratory medicine, 52(5), 439-451. https://doi.org/10.1093/labmed/lmaa110
Liu, Wei, et al. "MicroRNA-138 Regulates T-Cell Function by Targeting PD-1 in Patients with Hepatitis B Virus-Related Liver Diseases." Laboratory medicine vol. 52,5 (2021): 439-451. doi: https://doi.org/10.1093/labmed/lmaa110
Liu W, Zheng X, Wang J, He Q, Li J, Zhang Z, Liu H. MicroRNA-138 Regulates T-Cell Function by Targeting PD-1 in Patients with Hepatitis B Virus-Related Liver Diseases. Lab Med. 2021 Sep 01;52(5):439-451. doi: 10.1093/labmed/lmaa110. PMID: 33410459.
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Lab Med. 2021 Sep 01;52(5):439-451. doi: 10.1093/labmed/lmaa110.

MicroRNA-138 Regulates T-Cell Function by Targeting PD-1 in Patients with Hepatitis B Virus-Related Liver Diseases.

Laboratory medicine

Wei Liu, Xianzhao Zheng, Jie Wang, Quanli He, Junmin Li, Zengzeng Zhang, Hongchun Liu

Affiliations

  1. Department of Clinical Laboratory, The People's Hospital of Jiaozuo, China.
  2. Department of Nephrology, The Affiliated Hospital of Henan Polytechnic University, China.
  3. Department of Clinical Laboratory, The First Affiliated Hospital of Zhengzhou University, China.

PMID: 33410459 DOI: 10.1093/labmed/lmaa110

Abstract

OBJECTIVE: T-cell exhaustion in hepatitis B virus (HBV) infection, which results from upregulation of programmed cell death-1 (PD-1), leads to persistent HBV infection and related disease progression. Therefore, agents targeting PD-1 may prove beneficial in the treatment of this condition. MicroRNA-138 (miR-138) possesses an anti-tumor ability in that it targets immune checkpoints, including PD-1. However, the function and underlying mechanisms of miR-138 in patients with HBV infection remains unclear.

METHODS: Specimens were collected from healthy volunteers (n = 43) and patients with chronic hepatitis B (CHB; n = 52), liver cirrhosis (LC; n = 26), and hepatocellular carcinoma (HCC; n = 31); carriers of HBV who were asymptomatic (n = 51); and patients with CHB receiving antivirus treatment (n = 11). These specimens were then used to study the expression and relationship among miR-138, PD-1, and HBV DNA viral load. To investigate the role of miR-138 in regulating PD-1 expression and determine the effect of miR-138 in regulating T-cell function, a luciferase assay and a transfection assay were each performed with primary CD3+ T cells.

RESULTS: We found that PD-1 was upregulated and miR-138 was downregulated in patients with CHB, LC, and HCC. Correlations analysis revealed that PD-1 expression was positively correlated with HBV DNA viral load whereas miR-138 was negatively correlated. Luciferase assay results showed that miR-138 directly inhibited PD-1 expression by interacting with the 3'-untranslated region of PD-1. As a result of miR-138 overexpression in primary T cells, PD-1 in these T cells was downregulated and antivirus cytokines secreted by T cells were significantly upregulated. In addition, the expression levels of PD-1 and miR-138 were reversed in patients with CHB who received antivirus treatments.

CONCLUSION: Results showed that miR-138 can promote T-cell responses within patients with HBV infection by inducing a PD-1 blockade. Such an effect suggests that miR-138 may serve as a new therapeutic target for the treatment of HBV infection.

© American Society for Clinical Pathology 2021. All rights reserved. For permissions, please e-mail: [email protected].

Keywords: HBV-related liver diseases; PD-1; T cells; miR-138

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