Abstract
The Long arm of chromosome 20 (20q) is closely related to the development of colorectal cancer, so identifying the expression profile of genes on 20q through a comprehensive overview is indispensable. In this article, preliminar experimental data, several available databases and bioinformatics tools such as the Cancer Genome Atlas, the Encyclopedia of DNA Elements, the JASPAR database and starBase were combined to analyze the correlation between genes and chromosomal aberrations, microRNA and transcription factors, as well as to explore the expression feature and potential regulative mechanism. The results showed that the most frequently unregulated genes in colorectal cancer arelocated on chromosome 20q, present a significant CNA–mRNA correlation.Furthermore, the genes with mRNA overexpression showed co-expression features and tended to be clustered within the same genomic neighborhoods. Then, several genes were selected to carry out further analysis and demonstrated that shared transcription factors, a conserved bidirectional promoter, and competition for a limited pool of microRNAin the 3’UTR of mRNA may be the underlying mechanisms behind the co-expression of physically adjacent genes.Finally, the databases, Lentivirus shRNA, and qPCR were used to find that these adjacent genes with co-expression cooperatively participated in the same biological pathways associated with the pathogenesis and development of colorectal cancer.
Highlights
Chromosomal aberrations are presented in about 85% of colorectal cancer (CRC) patients and occur as nonrandom events, generally involving losses in 8p, 17p and 18q, and gain in 7p, 7q, 8q, 13q and 20q [1]
Once the somatic mutations of all genes in colon adenocarcinoma were analyzed by COSMIC, the result showed that the majority of top 20 genes with somatic mutations are mRNA over expression (18/20) and CNA gain, except 2 genes (PCLO with high methylation and APC with high point mutation)
When the somatic mutations was only restricted to “Gene expression”, we found that the top 20 genes mainly presented mRNA overexpression and CNA gain, and all were located on 20q, as shown through NCBI and Ensemble identification (Supplementary Figure 1)
Summary
Chromosomal aberrations are presented in about 85% of colorectal cancer (CRC) patients and occur as nonrandom events, generally involving losses in 8p, 17p and 18q, and gain in 7p, 7q, 8q, 13q and 20q [1]. The vast amount of molecular data involving genomes, transcriptomes, proteomes and resources from other biological layers are publicly available [6, 7], So in this study, several available databases, bioinformatics tools, preliminarexperimental data were reasonably combined and employed to analyze the correlation between genes located on 20q, CNA, microRNA, transcription, and so forth Through this comprehensive comparison method, we were able to explore the expression characteristics and potential regulative mechanisms of these genes, through which we can better understand the molecular basis of how these genes on 20q were involved in CRC, and identify novel genomic targets for therapeutic intervention
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