Authors
Zohreh Hashemian, Morteza Zarrabi, Masoumeh Nouri, Abbas Piryaei, Ali Mohammad Moradi, Mohssen Nassiri Toosi, Sara Taleahmad, Mustapha Najimi, Massoud Vosough
Published in
Journal of liver cancer. Aug 21, 2026. Epub Aug 21, 2026.
Abstract
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 (HNF4α) could improve the metabolic performance of Huh7-based three-dimensional hepatic microtissues.
Decellularized liver extracellular matrix-derived microparticles were incorporated into three-dimensional microtissues containing Huh7 cells, human umbilical vein endothelial cells, and Wharton's jelly mesenchymal stem cells using AggreWell technology. Experimental microtissues were generated with Huh7 cells expressing a SINEUP-based long noncoding RNA targeting HNF4α and were compared with control microtissues.
Enhanced HNF4α expression upregulated hepatic markers including HNF4α 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.
SINEUP-mediated enhancement of HNF4α 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.
PMID:
42625329
Bibliographic data and abstract were imported from PubMed on 21 Aug 2026.
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