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Potentials as biomarker and therapeutic target of upregulated long non-coding RNA HLA-F antisense RNA 1 in hepatitis B virus-associated hepatocellular carcinoma

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Abstract

The tissue-specific characteristics have encouraged researchers to identify organ-specific lncRNAs as disease biomarkers. This study aimed to identify the clinical and functional roles of long non-coding RNA HLA-F antisense RNA 1 (HLA-F-AS1) in hepatitis B virus (HBV)-hepatocellular carcinoma (HCC). A total of 121 HBV-HCC, 81 chronic hepatitis B (CHB), and 85 normal liver tissues were evaluated in this study. Real-time quantitative PCR assay was used to evaluate the RNA expression levels. Performance in diagnosis was compared between alpha fetoprotein (AFP) and HLA-F-AS1 using Receiver Operating Characteristic (ROC) curves. Performance in post-hepatectomy prognosis with high or low HLA-F-AS1 was compared using Kaplan–Meier curves. Multi-variable analysis was used to determine the informative predictors. Downstream miRNAs for HLA-F-AS1 were predicted and miR-128-3p was confirmed by luciferase reporter assay and RNA pull-down assay. In vitro functional analysis was performed by MTS reagent for cell proliferation and transwell assay for cell migration. HLA-F-AS1 levels were significantly increased in the HBV-HCC compared to normal healthy tissue and CHB tissues. HLA-F-AS1 exhibited a well potential in making a distinction between HBV-HCC and health, as well as HBV-HCC and CHB. The survival analysis revealed that patients with high levels of HLA-F-AS1 tend to shorter overall survival times. The best prognostic performance was achieved by HLA-F-AS1 after multi-variable analysis (HR 2.290, 95% CI 1.191–4.403, p = 0.013). Functional analysis showed that HLA-F-AS1 promoted cell proliferation and migration via miR-128-3p. Up-regulation of HLA-F-AS1 could serve as a promising diagnostic and prognostic marker for HBV-HCC after surgery, maybe useful in the management of HBV-HCC patients. HLA-F-AS1 can promote the progression of HBV-HCC, may be useful in the targeting treatment of HBV-HCC patients.

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Data availability

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Funding

The present study was supported by 2021 Scientific Research Topics of Heilongjiang Provincial Health and Wellness Committee (Grant No.: 20210303030052), 2021 Heilongjiang Provincial Universities Fundamental Research Funds Research Project (Basic Research Project of Basic Scientific Research Operating Expenses of Heilongjiang Provincial Department of Education) (Grant No.: 2021-KYYWF-0599).

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Author notes

  1. Xuemei Zhang and Wei Li have contributed equally to this work.

Authors and Affiliations

  1. Department of Gastroenterology, First Affiliated Hospital of Jiamusi University, Jiamusi, 154002, Heilongjiang, China

    Xuemei Zhang, Wei Li, Shuang Li & Zhengwu Zhang

  2. School of Basic Medicine, Jiamusi University, No. 258, Xuefu Street, Xiangyang District, Jiamusi, 154000, Heilongjiang, China

    Wenqi Song

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  1. Xuemei Zhang
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Contributions

Conceptualization: Xuemei Zhang and Wenqi Song; Data curation: Wei Li, Shuang Li, and Zhengwu Zhang; Formal analysis: Wei Li, Shuang Li, and Zhengwu Zhang; Funding acquisition: Xuemei Zhang; Investigation: Wei Li, Shuang Li, and Zhengwu Zhang; Methodology: Xuemei Zhang, Wei Li, and Shuang Li; Project administration: Wenqi Song; Resources: Shuang Li and Zhengwu Zhang; Software: Zhengwu Zhang; Supervision: Wenqi Song; Writing of the original draft: Xuemei Zhang; Writing, reviewing, & editing of the manuscript: Wenqi Song. The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Corresponding author

Correspondence to Wenqi Song.

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All authors have completed the ICMJE uniform disclosure form. The authors have no conflicts of interest to declare.

Ethical approval

The study was approved by the Human Research Ethics Committee of First Affiliated Hospital of Jiamusi University and informed consent was obtained from all individual participants.

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Informed consent

The study was conducted in accordance with the Declaration of Helsinki (as revised in 2013).

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Edited by Juergen Richt.

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Zhang, X., Li, W., Li, S. et al. Potentials as biomarker and therapeutic target of upregulated long non-coding RNA HLA-F antisense RNA 1 in hepatitis B virus-associated hepatocellular carcinoma. Virus Genes (2024). https://doi.org/10.1007/s11262-024-02065-8

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