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The Dysregulation of Polyamine Metabolism in Colorectal Cancer Is Associated with Overexpression of c-Myc and C/EBPβ rather than Enterotoxigenic Bacteroides fragilis Infection.

Snezhkina AV, Krasnov GS, Lipatova AV, Sadritdinova AF, Kardymon OL, Fedorova MS, Melnikova NV, Stepanov OA, Zaretsky AR, Kaprin AD, Alekseev BY, Dmitriev AA, Kudryavtseva AV - Oxid Med Cell Longev (2016)

Bottom Line: We found no statistically significant associations between them.We found that two mediators of metabolic reprogramming, inflammation, and cell proliferation c-Myc and C/EBPβ may serve as regulators of polyamine metabolism genes (SMOX, AZIN1, MTAP, SRM, ODC1, AMD1, and AGMAT) as they are overexpressed in tumors, have binding site according to ENCODE ChIP-Seq data, and demonstrate strong coexpression with their targets.Thus, increased polyamine metabolism in CRC could be driven by c-Myc and C/EBPβ rather than ETBF infection.

View Article: PubMed Central - PubMed

Affiliation: Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow 119991, Russia.

ABSTRACT
Colorectal cancer is one of the most common cancers in the world. It is well known that the chronic inflammation can promote the progression of colorectal cancer (CRC). Recently, a number of studies revealed a potential association between colorectal inflammation, cancer progression, and infection caused by enterotoxigenic Bacteroides fragilis (ETBF). Bacterial enterotoxin activates spermine oxidase (SMO), which produces spermidine and H2O2 as byproducts of polyamine catabolism, which, in turn, enhances inflammation and tissue injury. Using qPCR analysis, we estimated the expression of SMOX gene and ETBF colonization in CRC patients. We found no statistically significant associations between them. Then we selected genes involved in polyamine metabolism, metabolic reprogramming, and inflammation regulation and estimated their expression in CRC. We observed overexpression of SMOX, ODC1, SRM, SMS, MTAP, c-Myc, C/EBPβ (CREBP), and other genes. We found that two mediators of metabolic reprogramming, inflammation, and cell proliferation c-Myc and C/EBPβ may serve as regulators of polyamine metabolism genes (SMOX, AZIN1, MTAP, SRM, ODC1, AMD1, and AGMAT) as they are overexpressed in tumors, have binding site according to ENCODE ChIP-Seq data, and demonstrate strong coexpression with their targets. Thus, increased polyamine metabolism in CRC could be driven by c-Myc and C/EBPβ rather than ETBF infection.

No MeSH data available.


Related in: MedlinePlus

Results of the qPCR expression analysis of genes involved in polyamine metabolism and inflammation regulation in paired colorectal cancer samples. Cell color indicates expression level change in tumor compared to normal: increase (orange) and decrease (blue). Genes are rearranged according to the similarity of expression profiles. Samples with a high concentration of enterotoxigenic B. fragilis DNA (>1000 copies per 1 ng of total DNA) are marked with an asterisk.
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fig2: Results of the qPCR expression analysis of genes involved in polyamine metabolism and inflammation regulation in paired colorectal cancer samples. Cell color indicates expression level change in tumor compared to normal: increase (orange) and decrease (blue). Genes are rearranged according to the similarity of expression profiles. Samples with a high concentration of enterotoxigenic B. fragilis DNA (>1000 copies per 1 ng of total DNA) are marked with an asterisk.

Mentions: Using RT-qPCR, we evaluated the relative expression level of 17 genes involved in polyamine metabolism and 4 genes mediating metabolic reprogramming, and the regulation of inflammatory response and cell proliferation: c-Myc (MYC), n-Myc (MYCN), Max, and C/EBPβ gene encoding CCAAT/enhancer binding protein (CEBPB). The results are given in Figure 2 (tumor/normal relative expression level) and Figure 3 (coexpression analysis coupled to ENCODE ChIP-Seq data).


The Dysregulation of Polyamine Metabolism in Colorectal Cancer Is Associated with Overexpression of c-Myc and C/EBPβ rather than Enterotoxigenic Bacteroides fragilis Infection.

Snezhkina AV, Krasnov GS, Lipatova AV, Sadritdinova AF, Kardymon OL, Fedorova MS, Melnikova NV, Stepanov OA, Zaretsky AR, Kaprin AD, Alekseev BY, Dmitriev AA, Kudryavtseva AV - Oxid Med Cell Longev (2016)

Results of the qPCR expression analysis of genes involved in polyamine metabolism and inflammation regulation in paired colorectal cancer samples. Cell color indicates expression level change in tumor compared to normal: increase (orange) and decrease (blue). Genes are rearranged according to the similarity of expression profiles. Samples with a high concentration of enterotoxigenic B. fragilis DNA (>1000 copies per 1 ng of total DNA) are marked with an asterisk.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4940579&req=5

fig2: Results of the qPCR expression analysis of genes involved in polyamine metabolism and inflammation regulation in paired colorectal cancer samples. Cell color indicates expression level change in tumor compared to normal: increase (orange) and decrease (blue). Genes are rearranged according to the similarity of expression profiles. Samples with a high concentration of enterotoxigenic B. fragilis DNA (>1000 copies per 1 ng of total DNA) are marked with an asterisk.
Mentions: Using RT-qPCR, we evaluated the relative expression level of 17 genes involved in polyamine metabolism and 4 genes mediating metabolic reprogramming, and the regulation of inflammatory response and cell proliferation: c-Myc (MYC), n-Myc (MYCN), Max, and C/EBPβ gene encoding CCAAT/enhancer binding protein (CEBPB). The results are given in Figure 2 (tumor/normal relative expression level) and Figure 3 (coexpression analysis coupled to ENCODE ChIP-Seq data).

Bottom Line: We found no statistically significant associations between them.We found that two mediators of metabolic reprogramming, inflammation, and cell proliferation c-Myc and C/EBPβ may serve as regulators of polyamine metabolism genes (SMOX, AZIN1, MTAP, SRM, ODC1, AMD1, and AGMAT) as they are overexpressed in tumors, have binding site according to ENCODE ChIP-Seq data, and demonstrate strong coexpression with their targets.Thus, increased polyamine metabolism in CRC could be driven by c-Myc and C/EBPβ rather than ETBF infection.

View Article: PubMed Central - PubMed

Affiliation: Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow 119991, Russia.

ABSTRACT
Colorectal cancer is one of the most common cancers in the world. It is well known that the chronic inflammation can promote the progression of colorectal cancer (CRC). Recently, a number of studies revealed a potential association between colorectal inflammation, cancer progression, and infection caused by enterotoxigenic Bacteroides fragilis (ETBF). Bacterial enterotoxin activates spermine oxidase (SMO), which produces spermidine and H2O2 as byproducts of polyamine catabolism, which, in turn, enhances inflammation and tissue injury. Using qPCR analysis, we estimated the expression of SMOX gene and ETBF colonization in CRC patients. We found no statistically significant associations between them. Then we selected genes involved in polyamine metabolism, metabolic reprogramming, and inflammation regulation and estimated their expression in CRC. We observed overexpression of SMOX, ODC1, SRM, SMS, MTAP, c-Myc, C/EBPβ (CREBP), and other genes. We found that two mediators of metabolic reprogramming, inflammation, and cell proliferation c-Myc and C/EBPβ may serve as regulators of polyamine metabolism genes (SMOX, AZIN1, MTAP, SRM, ODC1, AMD1, and AGMAT) as they are overexpressed in tumors, have binding site according to ENCODE ChIP-Seq data, and demonstrate strong coexpression with their targets. Thus, increased polyamine metabolism in CRC could be driven by c-Myc and C/EBPβ rather than ETBF infection.

No MeSH data available.


Related in: MedlinePlus