Cell Cycle Regulation and DNA Damage Response Networks in Diffuse- and Intestinal-Type Gastric Cancer

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...

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Bibliographic Details
Published in:Cancers 2021-11, Vol.13 (22), p.5786
Main Authors: Tanabe, Shihori, Quader, Sabina, Ono, Ryuichi, Cabral, Horacio, Aoyagi, Kazuhiko, Hirose, Akihiko, Yokozaki, Hiroshi, Sasaki, Hiroki
Format: Article
Language:English
Subjects:
BRCA1 protein
Cell cycle
Cyclin-dependent kinases
Deoxyribonucleic acid
DNA
DNA damage
Drug resistance
Epstein-Barr virus
Gastric cancer
Gene expression
Genomes
Genomics
Intestine
Kinases
Malignancy
Mesenchyme
Metastasis
MicroRNAs
miRNA
Phase transitions
S phase
Stem cells
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Summary: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 G1/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 G1/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 G1/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.
ISSN:2072-6694
2072-6694
DOI:10.3390/cancers13225786