The relative quantity of miR-184 was determined in human glioma cell lines, and the expression of hypoxia-inducible factor-1 alpha (HIF-1α) was explored using western blotting.
These results suggest that miR-183 upregulation in malignant gliomas induces HIF-1α expression by targeting IDH2 and may play a role in glioma biology.
Surprisingly, we observed that PEITC suppressed the HIF-1α accumulation during hypoxia in human glioma U87, human prostate cancer DU145, colon cancer HCT116, liver cancer HepG2, and breast cancer SkBr3 cells.
The results of our analysis demonstrate that the combination of genes participating in the glycolytic process (ALDOA, ALDOC, ENO2, GAPDH, HK2, LDHA, LDHB, MDH1, PDHB, PFKM, PGI, PGK1, PGM1 and PKLR) with the already known tumor suppressors (PTEN, Rb, TP53), oncogenes (CDK4, EGFR, PDGF) and HIF-1, enhance the discrimination of low versus high-grade gliomas providing high prediction ability in a cross-validated framework.
Glioma derived isocitrate dehydrogenase-2 mutations induced up-regulation of HIF-1α and β-catenin signaling: possible impact on glioma cell metastasis and chemo-resistance.
Several theories have been proposed, including: increased angiogenesis because of accumulation of HIF-1α; a glioma CpG island methylator phenotype (G-CIMP) induced by inhibition of TET2; and increased vulnerability to oxidative stress because of depletion of antioxidants.
Finally, expression profiling experiments in glioma cells provided detailed insight into a broad range of specific biological pathways and processes downstream of HIF-1alpha.
Systemic administration of a therapeutic anti-HIF-1alpha siRNA with the peptide-targeted delivery systems resulted in significant tumor growth inhibition than a nontargeted delivery system or free siRNA via intravenous injection in nude mice bearing human glioma U87 xenografts.
Here we present methods for investigating the role of HIF-1alpha in glioma growth in vivo and in vitro using RNA interference in U251, U87, and U373 glioma cells.
To evaluate the effect of silencing HIF-1alpha in human glioma T98G cells, cells were transfected with HIF-1alpha-small interference RNA (HIF-1alpha-siRNA) and cultured under hypoxic conditions.
Introducing HIF-1alpha-targeted small interfering RNA (HIF-1alpha siRNA) into the glioma cell lines resulted in downregulation of HIF-1alpha expression, and significantly suppressed glioma cell migration in vitro.
We found that RNAi can be used to significantly attenuate glioma growth by reducing HIF-1alpha levels constitutively using short hairpin RNAs and transiently using small interfering RNAs (siRNA).
Given its low toxicity profile, its demonstrated antitumor activity in several animal models of cancer and its potential to inhibit the HIF-1 pathway, noscapine should be considered as an antiangiogenic chemotherapy for glioma.