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Development of hepatocellular carcinoma organoid model recapitulating HIF-1A metabolic signature.


ABSTRACT: Hypoxia is one of the main hallmarks of hepatocellular carcinoma (HCC) resulting from improper oxygenation and insufficient nourishment of the HCC microenvironment. The effect of hypoxia is mediated by hypoxia-inducible factor-1A (HIF-1A) via targeting various downstream pathways, including glycolysis, angiogenesis, and survival signaling. However, HCC cell lines in a 2-dimensional (2D) setting do not resemble the metabolic signature of HCC. Here we aim to overcome these limitations by developing an HCC organoid that recapitulates the HIF-1A metabolic shift. The enrichment analysis of the RNA-Seq data revealed that HIF-1A-driven glycolytic shift is of the significant pathways. The established organoid model, using xeno-free plasma-derived extracellular matrix (ECM) as a scaffold and nutrit

SUBMITTER: Khedr MA 

PROVIDER: S-EPMC11579110 | biostudies-literature | 2024 Nov

REPOSITORIES: biostudies-literature