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ORIGINAL RESEARCH article

Front. Microbiol.
Sec. Infectious Agents and Disease
Volume 15 - 2024 | doi: 10.3389/fmicb.2024.1499216
This article is part of the Research Topic MicroRNA: the swift development in infectious diseases View all 4 articles

MicroRNA-3145-3p Is a HBV Suppressor Induced by Endoplasmic Reticulum Stress During Viral Infection MicroRNA-3145 as a Potential Therapeutic Target for Hepatitis B Virus: Inhibition of Viral Replication via Downregulation of HBS and HBX

Provisionally accepted
Amrizal Muchtar Amrizal Muchtar 1Daichi Onomura Daichi Onomura 2Dan Ding Dan Ding 3Hironori Nishitsuji Hironori Nishitsuji 4Kunitada Shimotohno Kunitada Shimotohno 5Shunpei Okada Shunpei Okada 6Keiji Ueda Keiji Ueda 7Koichi Watashi Koichi Watashi 8Takaji Wakita Takaji Wakita 8Kei Iida Kei Iida 9Hironori Yoshiyama Hironori Yoshiyama 6Hisashi Iizasa Hisashi Iizasa 6*
  • 1 Faculty of Medicine, Muslim University of Indonesia, Makassar, Indonesia
  • 2 Division of Virology, Department of Infection and Immunity, Faculty of Medicine, Jichi Medical University, Shimotsuke, Japan
  • 3 Department of Pathology, Changhai Hospital, Naval Medical University, Shanghai, China
  • 4 Department of Virology and Parasitology, Fujita Health University School of Medicine, Toyoake, Japan
  • 5 Genome Medical Sciences Project, National Center for Global Health and Medicine, Ichikawa, Japan
  • 6 Faculty of Medicine, Shimane University, Izumo, Shimane, Japan
  • 7 Graduate School of Medicine, Osaka University, Suita, Ōsaka, Japan
  • 8 National Institute of Infectious Diseases (NIID), Tokyo, Tôkyô, Japan
  • 9 Kindai University, Higashi-osaka, Ōsaka, Japan

The final, formatted version of the article will be published soon.

    Current treatments for hepatitis B virus (HBV), such as interferons and nucleic acid analogs, have limitations due to side effects like depression and the development of drug-resistant mutants, highlighting the need for new therapeutic approaches. In this study, we identified microRNA-3145 (miR-3145) as a host-derived miRNA with antiviral activity that is upregulated in primary hepatocytes during HBV infection. The expression of its precursor, pri-miR-3145, increased in response to the virus, and miR-3145 downregulated the hepatitis B virus S (HBS) antigen and hepatitis B virus X (HBX), thereby inhibiting viral replication. The binding site for miR-3145 was located in the HBV polymerase (pol) region, as experimentally confirmed. Moreover, overexpression of HBS and HBX induced pri-miR-3145 expression through endoplasmic reticulum stress. The expression of pri-miR-3145 showed a strong correlation with the Nance–Horan syndrome-like 1 (NHSL1) gene, as it is encoded within an intron of NHSL1, and higher NHSL1 expression in hepatocellular carcinoma patients with HBV infection was associated with better prognosis. These findings suggest that miR-3145-3p, along with small molecules targeting its binding sites, holds promise as a potential therapeutic candidate for HBV treatment.

    Keywords: Hepatitis B virus1, microRNA2, Endoplasmic Reticulum Stress3, anti-viral drug4, hepatocellular carcinoma5

    Received: 20 Sep 2024; Accepted: 02 Dec 2024.

    Copyright: © 2024 Muchtar, Onomura, Ding, Nishitsuji, Shimotohno, Okada, Ueda, Watashi, Wakita, Iida, Yoshiyama and Iizasa. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Hisashi Iizasa, Faculty of Medicine, Shimane University, Izumo, 693-8501, Shimane, Japan

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