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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

(a) Enterotoxigenic B. fragilis (ETBF) DNA copy number per 50 ng of total extracted DNA in paired samples of colorectal cancer (logarithmic scale). (b) SMOX expression level relatively to two reference genes: RPN1 and GUSB. The samples with high rates of ETBF colonization tend to have higher expression of SMOX, especially in normal tissue (compared to the other norms). However, no statistically significant correlation between SMOX expression and ETBF colonization was observed.
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fig1: (a) Enterotoxigenic B. fragilis (ETBF) DNA copy number per 50 ng of total extracted DNA in paired samples of colorectal cancer (logarithmic scale). (b) SMOX expression level relatively to two reference genes: RPN1 and GUSB. The samples with high rates of ETBF colonization tend to have higher expression of SMOX, especially in normal tissue (compared to the other norms). However, no statistically significant correlation between SMOX expression and ETBF colonization was observed.

Mentions: We analyzed 36 paired samples of primary colorectal carcinomas and adjacent normal tissues to quantify ETBF. Serial dilution of genomic DNA from ETBF was used as standard. At least one copy of ETBF DNA per 50 ng of total extracted DNA was detected in 8 paired tumor and adjacent normal samples, including three samples, which showed a significantly increased amount of the ETBF DNA (>1000 copies/1 ng of extracted DNA). Most of the tested samples (23/36) demonstrated less than a copy of bacterial DNA per 50 ng of total extracted DNA. Five samples were found to be ETBF-negative (Figure 1).


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)

(a) Enterotoxigenic B. fragilis (ETBF) DNA copy number per 50 ng of total extracted DNA in paired samples of colorectal cancer (logarithmic scale). (b) SMOX expression level relatively to two reference genes: RPN1 and GUSB. The samples with high rates of ETBF colonization tend to have higher expression of SMOX, especially in normal tissue (compared to the other norms). However, no statistically significant correlation between SMOX expression and ETBF colonization was observed.
© Copyright Policy - open-access
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4940579&req=5

fig1: (a) Enterotoxigenic B. fragilis (ETBF) DNA copy number per 50 ng of total extracted DNA in paired samples of colorectal cancer (logarithmic scale). (b) SMOX expression level relatively to two reference genes: RPN1 and GUSB. The samples with high rates of ETBF colonization tend to have higher expression of SMOX, especially in normal tissue (compared to the other norms). However, no statistically significant correlation between SMOX expression and ETBF colonization was observed.
Mentions: We analyzed 36 paired samples of primary colorectal carcinomas and adjacent normal tissues to quantify ETBF. Serial dilution of genomic DNA from ETBF was used as standard. At least one copy of ETBF DNA per 50 ng of total extracted DNA was detected in 8 paired tumor and adjacent normal samples, including three samples, which showed a significantly increased amount of the ETBF DNA (>1000 copies/1 ng of extracted DNA). Most of the tested samples (23/36) demonstrated less than a copy of bacterial DNA per 50 ng of total extracted DNA. Five samples were found to be ETBF-negative (Figure 1).

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