Taken together, our findings demonstrate for the first time that elevated FUBP1 promotes NB glycolysis and growth by targeting HIF1α rather than N-Myc, suggesting that FUBP1 is a novel and powerful oncogene in the development of NB independent of N-Myc and may have potential in the diagnosis and treatment of NB.
Moreover, BCO1 inhibited the metastatic potential of NB cells and suppressed the enzymatic activity and expression of MMPs, as well as expression of HIF-1α and its downstream targets.
In this study, we conducted a combined analysis of RNA expression and DNA methylation of neuroblastoma cells silenced or unsilenced for HIF1A expression, grown in normoxia and hypoxia conditions.
Both HIF-1α and HIF-2α expression levels have been shown to correlate to patient outcome in various tumor forms and in neuroblastoma, a solid childhood tumor of the sympathetic nervous system, in particular, HIF-2α marks a subpopulation of immature neural crest-like perivascularly located cells and associates with aggressive disease and distant metastasis.
Our results indicate that the immunohistochemistry analysis of the protein expression of PDK1, PHD3, and HIF-1α defines the hypoxic status of NB tumors and can be used as a simple and relevant tool to stratify high-risk patients.
In this study, mitochondrial DNA (mtDNA) enriched (SK-N-AS) and depleted (ρ⁰) cells of neuroblastoma were cultured in a hypoxic chamber to simulate a hypoxic condition and then the major components involved in mitochondrial related pathways, hypoxia-inducible factor 1α (HIF-1α) and reactive oxygen species (ROS) were measured.
Differential regulation of HIF-1α and HIF-2α in neuroblastoma: Estrogen-related receptor alpha (ERRα) regulates HIF2A transcription and correlates to poor outcome.
Taken together, our study shows that CoCl2 may induce the nNOS expression and NO production through a HIF-1α mechanism in neuroblastoma cells, which may provide a potential target for the treatment of neurological hypoxic disorders caused by NO dysregulation.
In NBL cell lines, the combination of all-trans retinoic acid (ATRA) with HIF1A or EPAS1 silencing led to an acquired glial-cell phenotype and enhanced expression of glial-cell differentiation markers.
We found that Ex-4 decreased the HIF-1α expression in the SH-SY5Y cell line and primary cortical neurons under hypoxic conditions, and this effect was reversed by cotreatment with exendin (9-39), a GLP-1R antagonist.
The influence of intermittent hypoxia and HIF-1α siRNA on migration of neuroblastoma cells and in vitro differentiation of RAW 264.7 cells were assessed.
In conclusion, the present study provides the first evidence that β-carotene may represent an effective chemotherapeutic agent by regulating the invasion and metastasis of neuroblastoma via HIF-1α.
In present study, we determined the promotion of HIF-1α and survivin in brain samples of a mouse model of hypoxic-ischemia and in neuroblastoma SH-SY5Y cells post hypoxia treatment.
The two NB cell lines with MYCN amplification exhibited a significantly higher HIF-1α expression level and ATP content compared to the two cell lines without MYCN amplification.
MDM2 is a key inhibitor of p53 and a positive activator of hypoxia-inducible factor-1α (HIF-1α) and vascular endothelial growth factor (VEGF) activity with an important role in neuroblastoma pathogenesis.
Thus, our results provide mechanistic insights explaining how MYCN-amplified neuroblastoma cells contend with hypoxic stress and paradoxically how hypoxia contributes to neuroblastoma aggressiveness through combinatorial effects of N-Myc and HIF-1α.
These data provide the first evidence that topotecan is a potent inhibitor of HIF-1alpha and HIF-2alpha subunits in hypoxic neuroblastoma cells, leading to decreased VEGF expression and angiogenic activity.
Recruitment of HIF-1alpha and HIF-2alpha to common target genes is differentially regulated in neuroblastoma: HIF-2alpha promotes an aggressive phenotype.
These data indicate that BDNF plays a role in regulating VEGF levels in neuroblastoma cells and that targeted therapies to BDNF/TrkB, PI3K, mTOR signal transduction pathways, and/or HIF-1alpha have the potential to inhibit VEGF expression and limit neuroblastoma tumor growth.
These results suggest that prolonged hypoxia leads to resistance to clinically relevant drugs in neuroblastoma and that therapies aimed at inhibiting HIF-1alpha function may be useful in overcoming drug resistance in this tumor.