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Journal of General Virology header logo Journal of General Virology

Volume 103, Issue 12

LncRNA NEAT1 regulates HCV-induced Hepatocellular carcinoma by modulating the miR-9-BGH3 axis No Access

Abstract

Chronic hepatitis C virus (HCV) infection is a leading cause of end-stage liver diseases, such as fibrosis, cirrhosis and hepatocellular carcinoma (HCC). Several cellular entities, including paraspeckles and their related components, are involved in viral pathogenesis and cancer progression. NEAT1 lncRNA is a major component of paraspeckles that has been linked to several malignancies. In this study, analysis of the Cancer Genome Atlas (TCGA) database and validation in HCV-induced HCC tissue and serum samples showed significantly high expression of NEAT1 in patients with liver cancer. Moreover, we found that NEAT1 levels increased upon HCV infection. To further understand the mechanism of NEAT1-induced HCC progression, we selected one of its targets, miR-9–5 p, which regulates BGH3 mRNA levels. Interestingly, miR-9–5 p levels were downregulated upon HCV infection, whereas BGH3 levels were upregulated. Additionally, partial NEAT1 knockdown increased miR-9–5 p levels and decreased BGH3 levels, corroborating our initial results. BGH3 levels were also upregulated in HCV-induced HCC and TCGA tissue samples, which could be directly correlated with NEAT1 levels. As a known oncogene, BGH3 is directly linked to HCC progression mediated by NEAT1. We also found that NEAT1 levels remained upregulated in serum samples from patients treated with direct-acting antivirals (DAA), indicating that NEAT1 might be a molecular trigger that promotes HCC development. Collectively, these findings provide molecular insights into HCV-induced HCC progression via the NEAT1-miR-9-BGH3 axis.

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  • Accepted:
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Keyword(s): hepatitis C virus , Hepatocellular carcinoma , LncRNA-NEAT1 , Paraspeckle upon HCV infection and Tumour suppressor microRNAs
Funding
This study was supported by the:
  • Council of Scientific & Industrial Research (Award CSIR-SRF)
    • Principle Award Recipient: SachinKumar Tripathi
  • Department of Science and Technology, India (Award JC-Bose- SB/S2/JCB-51/2013)
    • Principle Award Recipient: SaumitraDas
© 2022 The Authors
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/content/journal/jgv/10.1099/jgv.0.001809
2022-12-02
2025-04-30
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LncRNA NEAT1 regulates HCV-induced Hepatocellular carcinoma by modulating the miR-9-BGH3 axis
J. Gen. Virol. 103, 001809 (2022); https://doi.org/10.1099/jgv.0.001809
/content/journal/jgv/10.1099/jgv.0.001809
/content/journal/jgv/10.1099/jgv.0.001809
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