Dogs with spontaneous high-grade gliomas are being proposed as useful large animal pre-clinical models for the human disease. Hypoxia is a critical microenvironmental condition that is common in both canine and human high-grade gliomas and drives increased angiogenesis, chemo- and radioresistance, and acquisition of a stem-like phenotype. This effect can be mediated by the hypoxia-induced expression of microRNAs, small non-coding RNAs that can modulate gene expression through interference with mRNA translation. Using an in vitro model with three canine high-grade glioma cell lines (J3T, SDT3G, and G06A) exposed to 72 hours of 1.5% oxygen versus standard 20% oxygen, we examined the global hypoxamiR profile using small RNA sequencing and performed pathway analysis for targeted genes using both Panther and NetworkAnalyst. Important pathways include many that are well-established as being important in glioma biology, general cancer biology, hypoxia, angiogenesis, immunology, and stem-ness, among others. This work provides the first examination of the effect of hypoxia on miRNA expression in the context of canine glioma, and highlights important similarities with the human disease.
Less...