title: Identification of potential therapeutic targets for colorectal cancer by bioinformatics analysis.
abstract: The aim of the present study was to identify potential therapeutic targets for colorectal cancer (CRC). The gene expression profile GSE32323, containing 34 samples, including 17 specimens of CRC tissues and 17 of paired normal tissues from CRC patients, was downloaded from the Gene Expression Omnibus database. Following data preprocessing using the Affy and preprocessCore packages, the differentially-expressed genes (DEGs) between the two types of samples were identified with the Linear Models for Microarray Analysis package. Next, functional and pathway enrichment analysis of the DEGs was performed using the Database for Annotation Visualization and Integrated Discovery. The protein-protein interaction (PPI) network was established using the Search Tool for the Retrieval of Interacting Genes database. Utilizing WebGestalt, the potential microRNAs (miRNAs/miRs) of the DEGs were screened and the integrated miRNA-target network was built. A cohort of 1,347 DEGs was identified, the majority of which were mainly enriched in cell cycle-related biological processes and pathways. Cyclin-dependent kinase 1 (CDK1), cyclin B1 (CCNB1), MAD2 mitotic arrest deficient-like 1 (MAD2L1) and BUB1 mitotic checkpoint serine/threonine kinase B (BUB1B) were prominent in the PPI network, while the over-represented genes in the integrated miRNA-target network were SRY (sex determining region Y)-box 4 (SOX4; targeted by hsa-mir-129), v-myc avian myelocytomatosis viral oncogene homolog (MYC; targeted by hsa-let-7c and hsa-mir-145) and cyclin D1 (CCND1; targeted by hsa-let-7b).CDK1,CCNB1andCCND1were also associated with the p53 signaling pathway. Overall, several genes associated with the cell cycle and p53 pathway were identified as biomarkers for CRC.CDK1,CCNB1,MAD2L1,BUB1B,SOX4, collagen type I α2 chain andMYCmay play significant roles in CRC progression by affecting the cell cycle-related pathways, whileCDK1,CCNB1andCCND1may serve as crucial regulators in the p53 signaling pathway. Furthermore,SOX4,MYCandCCND1may be targets of miR-129, hsa-mir-145 and hsa-let-7c, respectively. However, further validation of these data is required.
authors.affiliation: Department of General Surgery, Beijing Tiantan Hospital, Capital Medical University, Beijing 100050, P.R. China.
authors.forename: Ming
authors.initials: M
authors.lastname: Yan
authors.affiliation: Department of General Surgery, Beijing Tiantan Hospital, Capital Medical University, Beijing 100050, P.R. China.
authors.forename: Maomin
authors.initials: M
authors.lastname: Song
authors.affiliation: Department of General Surgery, Beijing Tiantan Hospital, Capital Medical University, Beijing 100050, P.R. China.
authors.forename: Rixing
authors.initials: R
authors.lastname: Bai
authors.affiliation: Department of General Surgery, Beijing Tiantan Hospital, Capital Medical University, Beijing 100050, P.R. China.
authors.forename: Shi
authors.initials: S
authors.lastname: Cheng
authors.affiliation: Department of General Surgery, Beijing Tiantan Hospital, Capital Medical University, Beijing 100050, P.R. China.
authors.forename: Wenmao
authors.initials: W
authors.lastname: Yan
keywords: cell cycle; colorectal cancer; differentially-expressed gene; miRNA-target network; p53 pathway; protein-protein interaction network