ABSTRACT
BACKGROUND: Colorectal cancer (CRC) is a common cancer with high morbidity and mortality. However, its molecular mechanism is not clear, nor the genes related to CRC stages. METHODS: Gene expression data in CRC and healthy colorectal tissues were obtained from gene expression omnibus. Limma package was used to identify the differentially expressed genes (DEGs) between control and CRC (stage I, II, III, and IV), obtaining 4 DEG sets. VennPlex was utilized to find all DEGs and intersection DEGs. Functional interactions between all DEGs and protein-protein interactions (PPIs) between intersection DEGs were analyzed using ReactomeFIViz and STRING, respectively, and networks were visualized. Known CRC-related genes were down-loaded from Comparative Toxicogenomics Database and mapped to PPI network. RESULTS: Totally, 851, 760, 729, and 878 DEGs were found between control and CRC stage I, II, III, and IV, respectively. Taken together, 1235 DEGs were found, as well as 128 up-regulated intersection DEGs, 365 down-regulated intersection DEGs, and 0 contra-regulated DEG. A functional interaction network of all DEGs and a PPI network of intersection DEGs were constructed, in which CDC20, PTTG1, and MAD2L1 interacted with BUB1B; UGT2B17 interacted with ADH1B; MCM7 interacted with MCM2. BUB1B, ADH1B, and MCM2 were known CRC-related genes. Gradually upregulated expressions of CDC20, PTTG1, MAD2L1, UGT2B17, and MCM7 in stage I, II, III, and IV CRC were confirmed by using quantitative PCR. Besides, up-regulated intersection DEGs enriched in pathways about Cell cycle, DNA replication, and p53 signaling. CONCLUSION: CDC20, PTTG1, MAD2L1, UGT2B17, and MCM7 might be CRC stage-related genes.
Subject(s)
Colorectal Neoplasms/genetics , Colorectal Neoplasms/pathology , Gene Expression Profiling , Adaptor Proteins, Signal Transducing/analysis , Adaptor Proteins, Signal Transducing/genetics , Adaptor Proteins, Signal Transducing/metabolism , Cdc20 Proteins/analysis , Cdc20 Proteins/genetics , Cdc20 Proteins/metabolism , Cell Cycle Proteins/analysis , Cell Cycle Proteins/genetics , Cell Cycle Proteins/metabolism , Databases, Genetic , Gene Expression Regulation, Neoplastic , Glucuronosyltransferase/analysis , Glucuronosyltransferase/genetics , Glucuronosyltransferase/metabolism , Humans , Minichromosome Maintenance Complex Component 7/analysis , Minichromosome Maintenance Complex Component 7/genetics , Minichromosome Maintenance Complex Component 7/metabolism , Minor Histocompatibility Antigens/analysis , Minor Histocompatibility Antigens/genetics , Minor Histocompatibility Antigens/metabolism , Neoplasm Staging , Nuclear Proteins/analysis , Nuclear Proteins/genetics , Nuclear Proteins/metabolism , Protein Interaction Maps , Securin/analysis , Securin/genetics , Securin/metabolismABSTRACT
OBJECTIVE: This study aims to investigate the molecular mechanism of injury development in the cortex and the striatum after cerebral ischemia/reperfusion (I/R). METHODS: Gene expression data (GSE23160) in the cortex and the striatum of an intraluminal middle cerebral artery occlusion-I/R mouse model (N = 12) and sham controls (N = 4) were downloaded from the Gene Expression Omnibus. Limma package was used to identify the differentially expressed genes (DEGs) between the I/R (2, 8, and 24 hours) and control groups. Correlation analysis was then performed to identify the highly correlated differentially expressed genes (HCDEGs). STRING and Cytoscape software were used to construct a protein-protein interaction (PPI) network of HCDEGs. Furthermore, Venny 2.0 was used to identify common overlapped DEGs whose transcription factors (TFs) were predicted using iRegulon in Cytoscape. RESULTS: For the cortex and the striatum, 2295 and 2282 DEGs were respectively identified between the I/R group and the controls, and were classified into 3 and 2 correlation modules. For each module, a PPI network was constructed, and Toll-like receptor 2 (Tlr2, degree = 25), interleukin 1ß (Il1b, degree = 21), and heme oxygenase-1 (Hmox1, degree = 17) had high connective degrees. Furthermore, 29 common overlapped DEGs were found across time and tissue, which might be targeted by 13 TFs. Especially, Tlr2, Il1b, and Hmox1 were targeted by myeloblastosis protein (Myb, target count = 16) and FBJ osteosarcoma protein (Fos, target count = 15). Moreover, plasminogen activator urokinase receptor (Plaur) was targeted by Fos, and it was an HCDEG in correlation modules of both cortex and striatum. Upregulation of Tlr2, Il1b, Hmox1, and Plaur in I/R injury was confirmed using quantitative polymerase chain reaction and immunohistochemical staining. CONCLUSION: Tlr2, Il1b, Hmox1, and Plaur regulated by Myb and Fos might participate in cortex and striatum injury after cerebral I/R.
