Tanabe Shihori, Quader Sabina, Ono Ryuichi, Cabral Horacio, Aoyagi Kazuhiko, Hirose Akihiko, Yokozaki Hiroshi, Sasaki Hiroki
Division of Risk Assessment, Center for Biological Safety and Research, National Institute of Health Sciences, Kawasaki 210-9501, Japan.
Innovation Center of NanoMedicine (iCONM), Kawasaki Institute of Industrial Promotion, Kawasaki 210-0821, Japan.
Cancers (Basel). 2021 Nov 18;13(22):5786. doi: 10.3390/cancers13225786.
Dynamic regulation in molecular networks including cell cycle regulation and DNA damage response play an important role in cancer. To reveal the feature of cancer malignancy, gene expression and network regulation were profiled in diffuse- and intestinal-type gastric cancer (GC). The results of the network analysis with Ingenuity Pathway Analysis (IPA) showed that the activation states of several canonical pathways related to cell cycle regulation were altered. The G/S checkpoint regulation pathway was activated in diffuse-type GC compared to intestinal-type GC, while canonical pathways of the cell cycle control of chromosomal replication, and the cyclin and cell cycle regulation, were activated in intestinal-type GC compared to diffuse-type GC. A canonical pathway on the role of BRCA1 in the DNA damage response was activated in intestinal-type GC compared to diffuse-type GC, where gene expression of BRCA1, which is related to G/S phase transition, was upregulated in intestinal-type GC compared to diffuse-type GC. Several microRNAs (miRNAs), such as mir-10, mir-17, mir-19, mir-194, mir-224, mir-25, mir-34, mir-451 and mir-605, were identified to have direct relationships in the G/S cell cycle checkpoint regulation pathway. Additionally, cell cycle regulation may be altered in epithelial-mesenchymal transition (EMT) conditions. The alterations in the activation states of the pathways related to cell cycle regulation in diffuse- and intestinal-type GC highlighted the significance of cell cycle regulation in EMT.
包括细胞周期调控和DNA损伤反应在内的分子网络动态调控在癌症中起着重要作用。为揭示癌症恶性特征，对弥漫型和肠型胃癌（GC）的基因表达和网络调控进行了分析。利用 Ingenuity Pathway Analysis（IPA）进行网络分析的结果表明，与细胞周期调控相关的几条经典通路的激活状态发生了改变。与肠型GC相比，G/S 检查点调控通路在弥漫型GC中被激活，而与染色体复制的细胞周期控制以及细胞周期蛋白和细胞周期调控相关的经典通路在肠型GC中比弥漫型GC更活跃。与弥漫型GC相比，BRCA1在DNA损伤反应中的作用相关的经典通路在肠型GC中被激活，其中与G/S期转换相关的BRCA1基因表达在肠型GC中比弥漫型GC上调。已确定几种 microRNA（miRNA），如mir-10、mir-17、mir-19、mir-194、mir-224、mir-25、mir-34、mir-451和mir-605，在G/S细胞周期检查点调控通路中具有直接关系。此外，上皮-间质转化（EMT）条件下细胞周期调控可能会改变。弥漫型和肠型GC中与细胞周期调控相关通路激活状态的改变突出了细胞周期调控在EMT中的重要性。
