Relationship between TIAM1 gene and epithelial-mesenchymal transition of colorectal cancer and bioinformatics analysis of TIAM1 gene related-miRNA

Abstract:

Objective：To explore the biological function of TIAM1 gene in colorectal cancer cells and its role in cell signaling network by doing bioinformatics analysis. Methods：Firstly，we forecasted the miRNA which interacted with TIAM1 by miRNA predicting tools；then analyzed the miRNA which related with the deletion of TIAM1 by expression profiles of colorectal cancer cell lines SW480 with deleted TIAM1；then selected the miRNA most possibly related with TIAM1 by synthesizing the intersection of the above two analyses. We clarified the signaling pathway participated by these target genes by predicting the target genes of hsa-mir-340 and doing pathway enrichment analysis. We made comparison between enrichment analysis results of target genes and results of proteins related with TIAM1. We clarified the signaling pathway situation which related with the deletion of TIAM1 by selecting the genes in sw480 cell lines with deleted TIAM1，whose expression profile logarithmic ratio was greater than 1 compared with that of wild type sw480 cell lines，and by analyzing the pathway enrichment of these genes. We analyzed the pathway enrichment for the protein in the protein-protein interaction network of TIAM1. We then analyzed the pathway enrichment for the protein which interacted with TIAM1 di－rectly and indirectly to epithelial mesenchymal transition（EMT） markers named E-cadherin and Vimentin. Results：Direct and indi－rect forecast demosnterated that microRNA hsa-mir-340 can interact with TIAM1 and coordinate with TIAM1 on the func－tion. Based on the analysis of SW480 with deleted TIAM1，ex－pressions of P53 signal pathway，DNA damage response，and Toll-like receptor signal pathway were up-regulated，indicating deleted TIAM1 may correlated with tumor inhibitory. According to the pathway analysis results，TIAM1 gene participated in a lot of signaling pathways such as the cell adhesion，cytoskeleton remodeling，cell proliferation and growth，etc and was possibly related with cancer development. TIAM1 and EMT markers E-cadherin and Vimentin regulatory network proteins were the signaling pathway members of transforming growth factor-β（TGF-β） receptor，androgen recep－tor，nuclear factor-?资B（NF-?资B），mitogen-activated protein kinase（MAPK），etc. These signaling pathways were possibly related with the occurrence of the EMT of colorectal cancer. Conclusions：Predicting hsa-mir-340 can regulate the expressions of TIAM1. TIAM1 deletion may correlate with tumor inhibitory and signaling pathway related with TIAM1 has close relationship with cancer metastasis. TIAM1 can influence the function of EMT markers E-cadherin and Vimentin and promote the colorectal cancer occurrence and metastasis by affecting EMT signaling pathways such as TGF-β receptor，androgen receptor，NF-kB，MAPK.