Ren Dongni, Yang Chen, Liu Nan, Wang Zhen, Wang Xin, Johnson Mark, Wang Wenshi, Zhang Pengxing, Yang Hongwei, Liu Hui, Cheng Yingduan, Wang Liang, Tu Yanyang
Department of Experimental Surgery, Tangdu Hospital, Fourth Military Medical University, Xi'an 710038, China.
J BUON. 2018 Jul-Aug;23(4):1136-1148.
In glioma, the sex-determining region Y-box 9 gene (SOX9) is overexpressed and its downregulation leads to inhibition of cell proliferation, invasion and increased cell apoptosis. To further evaluate the molecular and signal pathways associated with the function of SOX9 and SOX9 target genes, a global gene expression profile of the established SOX9-knockdown U251 cells was investigated.
The molecular function and biological pathways of differentially expressed genes (DEGs) were identified by gene ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. The interactome networks of DEGs were constructed using the STRING online tool. The genes were further validated by RT-qPCR.
GO analysis revealed that a set of 194 DEGs was shared in both the SOX9 KD-1 and SOX9 KD-2 U251 cells. GO analysis and KEGG pathway analysis showed that the DEGs were associated with biological processes involving cellular responses to hypoxia, osteoblast differentiation and angiogenesis, and special biological pathways, such as a TGF-beta signaling pathway and a HIF-1 signaling pathway. In addition, computational network of novel identified potential target genes linked to SOX9, including TGFB2, VEGFA, EGLN3 (PHD3), CA9 and HIF-1a. All of these genes were downregulated in the SOX9 knockdown U251 cells.
SOX9 may be a key regulator impacting the glioma cellular processes by influencing the cellular response to hypoxia and HIF-1 signaling pathway. TGFB2, VEGFA, EGLN3 (PHD3), CA9, and HIF-1a may be the target genes of SOX9.
在胶质瘤中，性别决定区Y盒9基因（SOX9）过表达，其下调导致细胞增殖、侵袭受到抑制，并增加细胞凋亡。为了进一步评估与SOX9功能及SOX9靶基因相关的分子和信号通路，我们研究了已建立的SOX9敲低U251细胞的全基因组表达谱。
通过基因本体论（GO）分析和京都基因与基因组百科全书（KEGG）通路分析来鉴定差异表达基因（DEG）的分子功能和生物学通路。使用STRING在线工具构建DEG的相互作用组网络。通过RT-qPCR进一步验证这些基因。
GO分析显示，在SOX9 KD-1和SOX9 KD-2 U251细胞中共有一组194个DEG。GO分析和KEGG通路分析表明，这些DEG与涉及细胞对缺氧的反应、成骨细胞分化和血管生成的生物学过程以及特定的生物学通路相关，如转化生长因子-β信号通路和低氧诱导因子-1信号通路。此外，新鉴定的与SOX9相关的潜在靶基因的计算网络，包括TGFB2、VEGFA、EGLN3（PHD3）、CA9和HIF-1α。所有这些基因在SOX9敲低的U251细胞中均下调。
SOX9可能是通过影响细胞对缺氧的反应和HIF-1信号通路来影响胶质瘤细胞进程的关键调节因子。TGFB2、VEGFA、EGLN3（PHD3）、CA9和HIF-1α可能是SOX9的靶基因。
