{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T06:48:58Z","timestamp":1791787738424,"version":"4.3.4"},"reference-count":50,"publisher":"Korean Liver Cancer Association","issue":"2","license":[{"start":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T00:00:00Z","timestamp":1787270400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004920","name":"Royan Institute","doi-asserted-by":"publisher","award":["402000234"],"award-info":[{"award-number":["402000234"]}],"id":[{"id":"10.13039\/501100004920","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["e-jlc.org"],"crossmark-restriction":true},"short-container-title":["JLC"],"published-print":{"date-parts":[[2026,9,30]]},"abstract":"<jats:p>Background\/Aims: Human liver cell-based drug-screening platforms require stable hepatocyte identity and metabolic competence, but Huh7 cells show reduced hepatic function. We investigated whether SINEUP-mediated enhancement of hepatocyte nuclear factor 4 alpha (HNF4\u03b1) could improve the metabolic performance of Huh7-based three-dimensional hepatic microtissues.Methods: Decellularized liver extracellular matrix-derived microparticles were incorporated into three-dimensional microtissues containing Huh7 cells, human umbilical vein endothelial cells, and Wharton\u2019s jelly mesenchymal stem cells using AggreWell technology. Experimental microtissues were generated with Huh7 cells expressing a SINEUP-based long noncoding RNA targeting HNF4\u03b1 and were compared with control microtissues.Results: Enhanced HNF4\u03b1 expression upregulated hepatic markers including HNF4\u03b1 and albumin, decreased alpha-fetoprotein and CDH2, increased CDH1 expression, suppressed glycolytic genes, modulated lipid metabolism, and increased cytochrome P450-related gene expression. Albumin and fibrinogen secretion, urea synthesis, and glycogen storage increased, whereas alpha-fetoprotein secretion, lactate production, and cell migration decreased.Conclusions: SINEUP-mediated enhancement of HNF4\u03b1 partially restored hepatocyte-like metabolic and functional properties in Huh7-based hepatic microtissues, supporting their potential use as an in vitro platform for drug discovery and toxicity screening.<\/jats:p>","DOI":"10.17998\/jlc.2026.05.13","type":"journal-article","created":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T01:02:10Z","timestamp":1787274130000},"page":"298-316","update-policy":"https:\/\/doi.org\/10.17998\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["SINEUP-mediated enhancement of HNF4\u03b1 improves metabolic function in Huh7-based bioengineered hepatic microtissues"],"prefix":"10.17998","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8365-2044","authenticated-orcid":true,"given":"Zohreh","family":"Hashemian","sequence":"first","affiliation":[{"name":"Department of Regenerative Medicine, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, Academic Center for Education, Culture and Research, Tehran, Iran"},{"name":"Department of Applied Cell Sciences, Faculty of Basic Sciences and Advanced Medical Technologies, Royan Institute, ACECR, Tehran, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1932-813X","authenticated-orcid":true,"given":"Morteza","family":"Zarrabi","sequence":"additional","affiliation":[{"name":"Research and Development Department, Royan Stem Cell Technology Company, Tehran, 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