title: 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.
authors.affiliation: Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow 119991, Russia.
authors.forename: Anastasiya V
authors.initials: AV
authors.lastname: Snezhkina
authors.affiliation: Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow 119991, Russia; Orekhovich Institute of Biomedical Chemistry, Russian Academy of Medical Sciences, Moscow 119121, Russia.
authors.forename: George S
authors.identifier: 0000-0002-6493-8378
authors.initials: GS
authors.lastname: Krasnov
authors.affiliation: Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow 119991, Russia.
authors.forename: Anastasiya V
authors.initials: AV
authors.lastname: Lipatova
authors.affiliation: Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow 119991, Russia; National Medical Research Center of Radiology, Ministry of Healthcare of the Russian Federation, Moscow 125284, Russia.
authors.forename: Asiya F
authors.initials: AF
authors.lastname: Sadritdinova
authors.affiliation: Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow 119991, Russia.
authors.forename: Olga L
authors.initials: OL
authors.lastname: Kardymon
authors.affiliation: Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow 119991, Russia.
authors.forename: Maria S
authors.initials: MS
authors.lastname: Fedorova
authors.affiliation: Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow 119991, Russia.
authors.forename: Nataliya V
authors.identifier: 0000-0001-8083-3018
authors.initials: NV
authors.lastname: Melnikova
authors.affiliation: Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow 119991, Russia.
authors.forename: Oleg A
authors.identifier: 0000-0001-6129-6499
authors.initials: OA
authors.lastname: Stepanov
authors.affiliation: Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow 117997, Russia.
authors.forename: Andrew R
authors.identifier: 0000-0002-7778-6617
authors.initials: AR
authors.lastname: Zaretsky
authors.affiliation: National Medical Research Center of Radiology, Ministry of Healthcare of the Russian Federation, Moscow 125284, Russia.
authors.forename: Andrey D
authors.initials: AD
authors.lastname: Kaprin
authors.affiliation: National Medical Research Center of Radiology, Ministry of Healthcare of the Russian Federation, Moscow 125284, Russia.
authors.forename: Boris Y
authors.identifier: 0000-0002-3398-4128
authors.initials: BY
authors.lastname: Alekseev
authors.affiliation: Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow 119991, Russia.
authors.forename: Alexey A
authors.identifier: 0000-0002-6827-9584
authors.initials: AA
authors.lastname: Dmitriev
authors.affiliation: Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow 119991, Russia; National Medical Research Center of Radiology, Ministry of Healthcare of the Russian Federation, Moscow 125284, Russia.
authors.forename: Anna V
authors.identifier: 0000-0002-3722-8207
authors.initials: AV
authors.lastname: Kudryavtseva
mesh_terms: D001442:Bacteroides Infections / Q000235:genetics / Q000378:metabolism / Q000382:microbiology / Q000473:pathology*; D001441:Bacteroides fragilis / Q000302:isolation & purification*; D022782:CCAAT-Enhancer-Binding Protein-beta / Q000096:biosynthesis* / Q000235:genetics; D015179:Colorectal Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000382:microbiology* / Q000473:pathology; D015870:Gene Expression; D016259:Genes, myc; D006801:Humans; D000587:Oxidoreductases Acting on CH-NH Group Donors / Q000096:biosynthesis / Q000235:genetics; D011073:Polyamines / Q000378:metabolism*; D016271:Proto-Oncogene Proteins c-myc / Q000096:biosynthesis* / Q000235:genetics; D000097667:Polyamine Oxidase
chemical_list: D022782:CCAAT-Enhancer-Binding Protein-beta; D000587:Oxidoreductases Acting on CH-NH Group Donors; D011073:Polyamines; D016271:Proto-Oncogene Proteins c-myc; D000097667:Polyamine Oxidase; C489427:MYC protein, human