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Downregulation of miR-483-5p (miR-483) is associated with the progression of hepatocellular carcinoma (HCC). However, the significant roles of miR-483 in nonalcoholic fatty liver disease (NAFLD), alcoholic fatty liver diseases (AFLD), and HCC remain elusive. In the current study, we investigated the biological significance of miR-483 in NAFLD, AFLD, and HCC in vitro and in vivo. The downregulation of miR-483 expression in HCC patients\u2019 tumor samples was associated with Notch 3 upregulation. Overexpression of miR-483 in a human bipotent progenitor liver cell line HepaRG and HCC cells dysregulated Notch signaling, inhibited cell proliferation\/migration, induced apoptosis, and increased sensitivity towards antineoplastic agents sorafenib\/regorafenib. Interestingly, the inactivation of miR-483 upregulated cell steatosis and fibrosis signaling by modulation of lipogenic and fibrosis gene expression. Mechanistically, miR-483 targets PPAR\u03b1 and TIMP2 gene expression, which leads to the suppression of cell steatosis and fibrosis. The downregulation of miR-483 was observed in mice liver fed with a high-fat diet (HFD) or a standard Lieber-Decarli liquid diet containing 5% alcohol, leading to increased hepatic steatosis\/fibrosis. Our data suggest that miR-483 inhibits cell steatosis and fibrogenic signaling and functions as a tumor suppressor in HCC. Therefore, miR-483 may be a novel therapeutic target for NAFLD\/AFLD\/HCC management in patients with fatty liver diseases and HCC.<\/jats:p>","DOI":"10.3390\/cancers15061715","type":"journal-article","created":{"date-parts":[[2023,3,13]],"date-time":"2023-03-13T03:03:57Z","timestamp":1678676637000},"page":"1715","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["MicroRNA-483-5p Inhibits Hepatocellular Carcinoma Cell Proliferation, Cell Steatosis, and Fibrosis by Targeting PPAR\u03b1 and TIMP2"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0613-9399","authenticated-orcid":false,"given":"Suryakant","family":"Niture","sequence":"first","affiliation":[{"name":"Julius L. Chambers Biomedical Biotechnology Research Institute, North Carolina Central University, Durham, NC 27707, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sashi","family":"Gadi","sequence":"additional","affiliation":[{"name":"Julius L. Chambers Biomedical Biotechnology Research Institute, North Carolina Central University, Durham, NC 27707, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qi","family":"Qi","sequence":"additional","affiliation":[{"name":"Julius L. Chambers Biomedical Biotechnology Research Institute, North Carolina Central University, Durham, NC 27707, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maxwell Afari","family":"Gyamfi","sequence":"additional","affiliation":[{"name":"The University of Tennessee Health Science Center, Department of Pharmaceutical Sciences, College of Pharmacy, Memphis, TN 38163, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rency S.","family":"Varghese","sequence":"additional","affiliation":[{"name":"Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, DC 20008, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4849-3399","authenticated-orcid":false,"given":"Leslimar","family":"Rios-Colon","sequence":"additional","affiliation":[{"name":"Julius L. Chambers Biomedical Biotechnology Research Institute, North Carolina Central University, Durham, NC 27707, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Uchechukwu","family":"Chimeh","sequence":"additional","affiliation":[{"name":"Julius L. Chambers Biomedical Biotechnology Research Institute, North Carolina Central University, Durham, NC 27707, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"family":"Vandana","sequence":"additional","affiliation":[{"name":"Julius L. Chambers Biomedical Biotechnology Research Institute, North Carolina Central University, Durham, NC 27707, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9296-2132","authenticated-orcid":false,"given":"Habtom W.","family":"Ressom","sequence":"additional","affiliation":[{"name":"Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, DC 20008, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0418-5116","authenticated-orcid":false,"given":"Deepak","family":"Kumar","sequence":"additional","affiliation":[{"name":"Julius L. Chambers Biomedical Biotechnology Research Institute, North Carolina Central University, Durham, NC 27707, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,3,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"723","DOI":"10.1002\/hep.29913","article-title":"Diagnosis, Staging, and Management of Hepatocellular Carcinoma: 2018 Practice Guidance by the American Association for the Study of Liver Diseases","volume":"68","author":"Marrero","year":"2018","journal-title":"Hepatology"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"7","DOI":"10.3322\/caac.21708","article-title":"Cancer statistics, 2022","volume":"72","author":"Siegel","year":"2022","journal-title":"CA Cancer J. 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