{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,14]],"date-time":"2026-01-14T16:47:35Z","timestamp":1768409255558,"version":"3.49.0"},"reference-count":41,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,1,6]],"date-time":"2025-01-06T00:00:00Z","timestamp":1736121600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100009619","name":"AMED","doi-asserted-by":"publisher","award":["21fk0310105h005"],"award-info":[{"award-number":["21fk0310105h005"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009619","name":"AMED","doi-asserted-by":"publisher","award":["21fk0310104h9905"],"award-info":[{"award-number":["21fk0310104h9905"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Microbiol."],"abstract":"<jats:p>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\u2013Horan syndrome-like 1 (<jats:italic>NHSL1<\/jats:italic>) 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.<\/jats:p>","DOI":"10.3389\/fmicb.2024.1499216","type":"journal-article","created":{"date-parts":[[2025,1,6]],"date-time":"2025-01-06T07:05:08Z","timestamp":1736147108000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["MicroRNA-3145 as a potential therapeutic target for hepatitis B virus: inhibition of viral replication via downregulation of HBS and HBX"],"prefix":"10.3389","volume":"15","author":[{"given":"Amrizal","family":"Muchtar","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daichi","family":"Onomura","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dan","family":"Ding","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hironori","family":"Nishitsuji","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kunitada","family":"Shimotohno","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shunpei","family":"Okada","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Keiji","family":"Ueda","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Koichi","family":"Watashi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takaji","family":"Wakita","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kei","family":"Iida","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hironori","family":"Yoshiyama","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hisashi","family":"Iizasa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2025,1,6]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"215","DOI":"10.1016\/j.cell.2009.01.002","article-title":"MicroRNAs: target recognition and regulatory functions","volume":"136","author":"Bartel","year":"2009","journal-title":"Cell"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"1327","DOI":"10.1016\/j.cell.2017.05.046","article-title":"Comprehensive and integrative genomic characterization of hepatocellular carcinoma","volume":"169","year":"2017","journal-title":"Cell"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"805","DOI":"10.1016\/j.ccell.2016.04.013","article-title":"Compounds triggering ER stress exert anti-melanoma effects and overcome BRAF inhibitor resistance","volume":"29","author":"Cerezo","year":"2016","journal-title":"Cancer Cell"},{"key":"ref4","doi-asserted-by":"publisher","first-page":"431","DOI":"10.1042\/BJ20102071","article-title":"Endoplasmic reticulum stress induced by hepatitis B virus X protein enhances cyclo-oxygenase 2 expression via activating transcription factor 4","volume":"435","author":"Cho","year":"2011","journal-title":"Biochem. 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