Identification of key regulators associated with colon cancer prognosis and pathogenesis

细胞周期蛋白依赖激酶1 BUB1型 小桶 生物 基因 微阵列分析技术 小RNA 计算生物学 微阵列 细胞周期 癌症研究 生物信息学 遗传学 基因表达 基因本体论 染色体 染色体分离
作者
Narges Toolabi,Fattane Sam Daliri,Amir Mokhlesi,Mahmood Talkhabi
出处
期刊:Journal of Cell Communication and Signaling [Springer Science+Business Media]
卷期号:16 (1): 115-127 被引量:19
标识
DOI:10.1007/s12079-021-00612-8
摘要

Colon cancer (CC) is the fourth deadliest cancer in the world. New insights into prognostication might be helpful to define the optimal adjuvant treatments for patients in routine clinical practice. Here, a microarray dataset with 30 primary tumors and 30 normal samples was analyzed using GEO2R to find differentially expressed genes (DEGs). Then, DAVID, KEGG, ChEA and X2K were used to analyze DEGs-related Gene Ontology, pathways, transcription factors (TFs) and kinases, respectively. Protein–protein interaction (PPI) networks were constructed using the STRING database and Cytoscape. The modules and hub genes of DEGs was determined through MCODE and CytoHubba plugins, and the expression of hub genes was verified using GEPIA. To find microRNAs and metabolites associated with DEGs, miRTarBase and HMDB were used, respectively. It was found that 233 and 373 genes were upregulated and downregulated in CC, respectively. GO analysis showed that the upregulated DEGs were mainly involved in mitotic nuclear division and cell division. Top 10 hub genes were identified, including AURKB, CDK1, DLGAP5, AURKA, CCNB2, CCNB1, BUB1B, CCNA2, KIF20A and BUB1. Whereas, FOMX1, E2F7, E2F1, E2F4 and AR were identified as top 5 TFs in CC. Moreover, CDK1, CDC2, MAPK14, ATM and CK2ALPHA was identified as top 5 kinases in CC. miRNAs analysis showed that Hsa-miR-215-5p hsa-miR-193b-3p, hsa-miR-192-5p and hsa-miR-16-5p could target the largest number of CC genes. Taken together, CC-related genes, especially the hub genes, TFs, and metabolites might be used as novel biomarkers for CC, as well as for diagnosis and guiding therapeutic strategies for CC.

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