Hypoxia-inducible factor-1α/interleukin-1β signaling enhances hepatoma epithelial-mesenchymal transition through macrophages in a hypoxic-inflammatory microenvironment.
We found that T3 treatment increased cellular and secreted FN in human hepatoma cells (HepG2) and human dermal fibroblasts (HF) via the PI3K/Akt/HIF-1 pathway.
Of the ten miRNAs predicted by the 3'-UTR of HIF-1α mRNA, PPIX treatment increased miR-199a-5p, leading to the inhibition of E2F3 expression which is upregulated in mesenchymal liver tumor. miR-199a-5p levels were downregulated in HCC with E2F3 overexpression.
Human hepatoma HepG2 cells were treated with various mitochondrial respiration inhibitors and an uncoupler, respectively, and the mRNA and protein expressions as well as transactivation activity of HIF-1α were determined.
These findings suggest that specific inhibition of HIF-1α expression in combination with radiotherapy would be expected to exert a strong antitumor effect on human hepatoma.
In this study, silibinin was found to inhibit hypoxia-induced HIF-1alpha accumulation and HIF-1 transcriptional activity in human cervical (HeLa) and hepatoma (Hep3B) cells.
Consistent with these observations, green fluorescent protein-HIF-1 alpha is differently distributed during hypoxia and reoxygenation in hepatoma and endothelial cells.
In this study, we investigated its effect on hypoxia-inducible factor-1a (HIF-1a) in rat pheochromacytoma (PC12), human osteosarcoma (HOS) and human hepatoma (HepG2) cells.
The pro-oxidants H2O2 and buthionine sulfoximine down-regulated HIF-1alpha and P-gp, whereas up-regulation was achieved with the radical scavengers dehydroascorbate, N-acetylcysteine, and vitamin E. The correlation of HIF-1alpha and P-gp expression was validated by the use of hepatoma tumor spheroids that were either wild type (Hepa1) or mutant (Hepa1C4) for aryl hydrocarbon receptor nuclear translocator (ARNT), i.e., HIF-1beta.
Reporter gene analyses with a series of nested deletion mutants of the hepatoma type II hexokinase promoter show that a significant fraction of the total activation observed under hypoxic conditions localizes to the distal region where the overlapping HIF-1/E-box sequences are located.
Hypoxic treatment of various mouse and human hepatoma cell lines led to the expected increase in the amount of PGK1 and PKM2 mRNA, while HIF-1alpha mRNA levels were not significantly elevated.
To analyse further the mechanisms underlying induction of the genes identified in the differential display, inducible expression was compared in wild-type mouse hepatoma cells (Hepa-1), and mutant derivatives (c4) which fail to generate HIF-1, due to a functional defect in one component, HIF-1 beta.Two types of response were defined.