Koehler Jennifer, Sandey Maninder, Prasad Nripesh, Levy Shawn A, Wang Xiaozhu, Wang Xu
Department of Pathobiology, Auburn University, Auburn, AL, United States.
HudsonAlpha Institute for Biotechnology, Huntsville, AL, United States.
Front Vet Sci. 2020 Feb 28;7:104. doi: 10.3389/fvets.2020.00104. eCollection 2020.
Dogs with spontaneous high-grade gliomas increasingly 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. Some of this effect is mediated by the hypoxia-induced expression of microRNAs, small (~22 nucleotides long), non-coding RNAs that can modulate gene expression through interference with mRNA translation. Using an model with three canine high-grade glioma cell lines (J3T, SDT3G, and G06A) exposed to 72 h of 1.5% oxygen vs. standard 20% oxygen, we examined the global "hypoxamiR" profile using small RNA-Seq 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.
自发性高级别胶质瘤犬越来越被认为是研究人类该疾病有用的大型动物临床前模型。缺氧是一种关键的微环境条件，在犬类和人类高级别胶质瘤中都很常见，它会促使血管生成增加、产生化学和放射抗性，并获得干细胞样表型。这种效应部分是由缺氧诱导的微小RNA（长度约22个核苷酸的小非编码RNA）表达介导的，微小RNA可通过干扰mRNA翻译来调节基因表达。我们使用一个模型，将三种犬高级别胶质瘤细胞系（J3T、SDT3G和G06A）分别暴露于1.5%氧气环境72小时和标准的20%氧气环境，通过小RNA测序检测整体“缺氧微小RNA”谱，并使用Panther和NetworkAnalyst对靶向基因进行通路分析。重要通路包括许多在胶质瘤生物学、一般癌症生物学、缺氧、血管生成、免疫学和干性等方面已被充分证实很重要的通路。这项工作首次研究了缺氧对犬胶质瘤中微小RNA表达的影响，并突出了与人类疾病的重要相似之处。
