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

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.

The role of microbiota in the development of colorectal cancer

“…It has been suggested that SMO acts as a potential source of inflammation‐associated ROS, which is produced during polyamine catabolism. This causes apoptosis, DNA damage, and consequently, the formation of cancer …”

“…This causes apoptosis, DNA damage, and consequently, the formation of cancer. 85 Streptococcus bovis/Streptococcus gallolyticus S. bovis is implicitly associated with an expanded of a variety of cell and molecular modifications that may be linked with the appearance of CRC. 86 The wall-extracted S. bovis antigen induces the expression of COX-2 ( Fig.…”

Mutational load in carotid body tumor

“…Tumor development is closely associated with the accumulation of somatic mutations, which may be due to various processes such as endogenous and exogenous DNA damage, defective mechanisms of DNA replication, modification, and repair [2,3]. These cause the changes in expression profiles of many genes, including activation of oncogenes and inactivation of tumor suppressor genes that lead to alterations in signaling pathways, cellular metabolism, and proliferation [4][5][6][7][8][9][10][11][12][13][14]. Distinct combinations of mutation types ("mutational signatures") depend on different mutation processes; multiple mutation processes generate jumbled composite signatures.…”

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“…qPCR procedure was performed as described. [20] PCR products were analyzed in 2% agarose gels, purified and submitted for Sanger sequencing on an ABI Prism 3100 Genetic Analyzer (Thermo Fisher Scientific, USA). qPCR data were analyzed using two reference genes, GUSB and RPN1, [21,22] and ΔΔCt-method with ATG program (Analysis of Transcription of Genes).…”