Journal of liver cancer · 2026
SINEUP-mediated enhancement of HNF4α improves metabolic function in Huh7-based bioengineered hepatic microtissues.
СтатьяНазвание и аннотация: Перевод пока не подготовлен
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Hashemian Zohreh, Zarrabi Morteza, Nouri Masoumeh, Piryaei Abbas, Moradi Ali Mohammad, Toosi Mohssen Nassiri, Taleahmad Sara, Najimi Mustapha, Vosough Massoud
Аннотация
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 (HNF4α) 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'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.
RESULTS: 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.
CONCLUSIONS: 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.
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: 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.