MicroRNA-3145 as a potential therapeutic target for hepatitis B virus: inhibition of viral replication via downregulation of HBS and HBX
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...
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| Format: | Article |
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Frontiers Media S.A.
2025-01-01
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| Series: | Frontiers in Microbiology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fmicb.2024.1499216/full |
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| author | Amrizal Muchtar Amrizal Muchtar Daichi Onomura Daichi Onomura Dan Ding Dan Ding Hironori Nishitsuji Kunitada Shimotohno Shunpei Okada Keiji Ueda Koichi Watashi Takaji Wakita Kei Iida Kei Iida Hironori Yoshiyama Hisashi Iizasa |
| author_facet | Amrizal Muchtar Amrizal Muchtar Daichi Onomura Daichi Onomura Dan Ding Dan Ding Hironori Nishitsuji Kunitada Shimotohno Shunpei Okada Keiji Ueda Koichi Watashi Takaji Wakita Kei Iida Kei Iida Hironori Yoshiyama Hisashi Iizasa |
| author_sort | Amrizal Muchtar |
| collection | DOAJ |
| description | 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 the virus infection, 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. |
| format | Article |
| id | doaj-art-e8761cbeee894857bb3a4d4db6ba9d70 |
| institution | Kabale University |
| issn | 1664-302X |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Microbiology |
| spelling | doaj-art-e8761cbeee894857bb3a4d4db6ba9d702025-01-23T13:39:42ZengFrontiers Media S.A.Frontiers in Microbiology1664-302X2025-01-011510.3389/fmicb.2024.14992161499216MicroRNA-3145 as a potential therapeutic target for hepatitis B virus: inhibition of viral replication via downregulation of HBS and HBXAmrizal Muchtar0Amrizal Muchtar1Daichi Onomura2Daichi Onomura3Dan Ding4Dan Ding5Hironori Nishitsuji6Kunitada Shimotohno7Shunpei Okada8Keiji Ueda9Koichi Watashi10Takaji Wakita11Kei Iida12Kei Iida13Hironori Yoshiyama14Hisashi Iizasa15Department of Microbiology, Faculty of Medicine, Shimane University, Izumo, JapanFaculty of Medicine, Universitas Muslim Indonesia, Makassar, IndonesiaDepartment of Microbiology, Faculty of Medicine, Shimane University, Izumo, JapanDivision of Virology, Department of Infection and Immunity, Jichi Medical University, Shimotsuke, JapanDepartment of Microbiology, Faculty of Medicine, Shimane University, Izumo, JapanDepartment of Pathology, Changhai Hospital, Naval Medical University, Shanghai, ChinaDepartment of Virology and Parasitology, Fujita Health University School of Medicine, Toyoake, JapanGenome Medical Sciences Project, National Center for Global Health and Medicine, Ichikawa, JapanDepartment of Microbiology, Faculty of Medicine, Shimane University, Izumo, JapanDivision of Virology, Department of Microbiology and Immunology, Osaka University Graduate School of Medicine, Suita, JapanDepartment of Virology II, National Institute of Infectious Diseases, Tokyo, JapanDepartment of Virology II, National Institute of Infectious Diseases, Tokyo, JapanFaculty of Science and Engineering, Kindai University, Higashiōsaka, Japan0Center for Cancer Immunotherapy and Immunobiology, Graduate School of Medicine, Kyoto University, Kyoto, JapanDepartment of Microbiology, Faculty of Medicine, Shimane University, Izumo, JapanDepartment of Microbiology, Faculty of Medicine, Shimane University, Izumo, JapanCurrent 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 the virus infection, 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.https://www.frontiersin.org/articles/10.3389/fmicb.2024.1499216/fullhepatitis B virusmicroRNAendoplasmic reticulum stressanti-viral drughepatocellular carcinoma |
| spellingShingle | Amrizal Muchtar Amrizal Muchtar Daichi Onomura Daichi Onomura Dan Ding Dan Ding Hironori Nishitsuji Kunitada Shimotohno Shunpei Okada Keiji Ueda Koichi Watashi Takaji Wakita Kei Iida Kei Iida Hironori Yoshiyama Hisashi Iizasa MicroRNA-3145 as a potential therapeutic target for hepatitis B virus: inhibition of viral replication via downregulation of HBS and HBX Frontiers in Microbiology hepatitis B virus microRNA endoplasmic reticulum stress anti-viral drug hepatocellular carcinoma |
| title | MicroRNA-3145 as a potential therapeutic target for hepatitis B virus: inhibition of viral replication via downregulation of HBS and HBX |
| title_full | MicroRNA-3145 as a potential therapeutic target for hepatitis B virus: inhibition of viral replication via downregulation of HBS and HBX |
| title_fullStr | MicroRNA-3145 as a potential therapeutic target for hepatitis B virus: inhibition of viral replication via downregulation of HBS and HBX |
| title_full_unstemmed | MicroRNA-3145 as a potential therapeutic target for hepatitis B virus: inhibition of viral replication via downregulation of HBS and HBX |
| title_short | MicroRNA-3145 as a potential therapeutic target for hepatitis B virus: inhibition of viral replication via downregulation of HBS and HBX |
| title_sort | microrna 3145 as a potential therapeutic target for hepatitis b virus inhibition of viral replication via downregulation of hbs and hbx |
| topic | hepatitis B virus microRNA endoplasmic reticulum stress anti-viral drug hepatocellular carcinoma |
| url | https://www.frontiersin.org/articles/10.3389/fmicb.2024.1499216/full |
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