Construction of key signal regulatory network in metastatic colorectal cancer

Abstract

There are many stages in the development and metastasis of colorectal cancer (CRC). In this study, we compared the differential expression genes in different stages of metastatic CRC. Then, we screened the continuously up-regulated genes and the continuously down-regulated genes that were associated with the development and metastasis of CRC. After analyzing the intersection of differential expression genes in each stage, we screened the continuously up-regulated genes and deviated genes in the extracellular matrix and the continuously down-regulated genes and deviated genes in the mitochrondia of CRC. Then, we performed gene ontology enrichment analysis of the deviated genes in different phases, and we found that key molecular events occurred in the period extending from stage II to III (early stage of metastasis) of CRC. Furthermore, in this period we found that the chemotaxis of inflammatory cells had decreased in the extracellular matrix. On the other hand, the aerobic respiration had increased in the mitochondrion. Then, we constructed protein-protein interaction network of deviated genes in the extracellular matrix and mitochondrion. We used the network module and hub network to analyze the protein-protein interaction network. The network module analysis showed that the protein complex of VEGFA and CCL7-CCR3 is the key node in the extracellular matrix, while MAPK1 is the key node in the mitochondrion. The hub network analysis showed that the signal transmission chain FN1→SPARC→COL1A1→MMP2 is the key regulatory pathway for extracellular signal transmission. Furthermore, it also showed that CAV1→MAPK3→RAF1→NR3C1→MAPK1→ESR1 is the key regulatory pathway for signal transmission in mitochondrion.

A network pharmacology-based investigation on the bioactive ingredients and molecular mechanisms of Gelsemium elegans Benth against colorectal cancer

“…Mitogen-activated protein kinase 3 (MAPK3) belongs to the protein kinase superfamily and catalyzes the concomitant phosphorylation of a threonine and a tyrosine residue in the MAP kinase p38. It has been confirmed to be a potential therapeutic target for different kinds of human cancers, including CRC [43][44][45][46][47]. A previous study revealed that phosphorylated AMP-activated protein kinase (AMPK) expression in CRC was associated with superior prognosis among p-MAPK3 positive cases, indicating a possible interaction between the AMPK and MAPK pathways influencing tumor behavior [46].…”

Effect of glucose deprivation on the expression of genes encoding glucocorticoid receptor and some related factors in ERN1-knockdown U87 glioma cells

“…There are data indicating that miR-124 might contribute to the glucocorticoid resistance by promoting the proliferation and inhibiting the apoptosis (Vonlanthen et al 2014;Kim et al 2015;Huang et al 2016;Liang et al 2017). Furthermore, it has also been shown that NR3C1 is a key component of the regulatory pathway for signal transmission in mitochondria and that glucocorticoids can stimulate directly the mitochondrial transcription by the mitochondrially localized glucocorticoid receptors (Minchenko and Germanyuk 1984;Minchenko 1988;Minchenko and Tronjko 1988;Psarra and Sekeris 2011;Qi and Ding, 2017). Moreover, glucocorticoid receptors can also be a signal by binding to other transcription factors and modulate the transcriptional regulation of target genes (Khan et al 2011;Li et al 2012;Dasgupta et al 2015).…”

Eotaxins and Their Receptor in Colorectal Cancer—A Literature Review

“…Other researchers have also indicated an important role of the complex between VEGF-A and CCL7-CCR3 axis as a key node in the extracellular matrix of CRC cells in early metastatic stages. They have demonstrated that chemotaxis of inflammatory cells during this period (from stage II to III TNM) decreases in extracellular matrix and it might be connected with the established connection between CCL7-CCR3 and metalloproteinases (MMPs)/chemotactic factor family [86].…”