Cumulative evidence has established that hypoxia-inducible factor-1α (HIF-1α) and its downstream target, vascular endothelial growth factor (VEGF), play a critical role in hepatocellular carcinoma angiogenesis, invasiveness and metastasis.
Decreased expression of SBP1 could promote tumor invasiveness by increasing GPX1 activity and diminishing HIF-1α expression in HCC; SBP1 could be a novel biomarker for predicting prognosis and guiding personalized therapeutic strategies, especially in patients with advanced HCC.
Expression of HIF1α mRNA was significantly upregulated in HCC tissues (<i>P</i><0.05 in all cases); this was supported by the results of the Western blotting (<i>P</i>=0.031) and IHC analyses.
Finally, clinical analysis confirmed the positive correlation between histone deacetylase 5 and hypoxia-inducible factor-1α in hepatocellular carcinoma specimens and a relatively poor prognosis for the patients with high levels of histone deacetylase 5 and hypoxia-inducible factor-1α.
Forced expression of Dicer prevented the hypoxia-induced increase in hypoxia-inducible factor 1α (HIF1α), HIF2α, hypoxia-inducible genes (CA9, glucose transporter 1), EMT markers, and cell migration.<b>Conclusions:</b> We here identify downmodulation of Dicer as novel essential process in hypoxia-induced EMT in HCC and demonstrate that induced expression of Dicer counteracted hypoxia-induced EMT.
Here, we present in vitro and in vivo evidence that the extremely high level of hypoxia-inducible factor-1α (HIF-1α) in hepatocellular carcinoma is intimately correlated with resistance to topoisomerase I inhibitors.
HIF-1α, LOXL2 expression and CD31/periodic acid-Schiff double staining in HCC patient samples were examined by immunohistochemical staining. shRNA plasmids against HIF-1α was used to determine whether LOXL2 been increased by HIF-1α.
However, our data point toward a significant function of HIF-1alpha in determining chemosensitivity of HCC and therefore warrant validation of HIF-1alpha-inhibitors as adjuvant therapeutic agents in clinical studies of human HCC.
Hsp27 was upregulated in HCC tissues, and Hsp27 overexpression significantly facilitated formation of HCC cell colony and invasion in normoxia and tolerance in hypoxia by interacting with HIF-1α.
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.
Hypoxic stimulation of HCC 97L cells increased the level of CTGF mRNA by 2.80-fold within 1.5 h, and hypoxia-inducible factor-1α mRNA levels in these cells could be increased by stimulation with recombinant CTGF protein.
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.
Immunohistochemistry for GLDC and HIF-1α was validated on two lung NSCC cell lines (A549, NCI-H460) and evaluated on a tissue microarray with 428 lung NSCC: 184 adenocarcinomas, 211 squamous cell carcinomas, and 33 large cell carcinomas (LCC).