The Impact of Diet on the Involvement of Non-Coding RNAs, Extracellular Vesicles, and Gut Microbiome-Virome in Colorectal Cancer Initiation and Progression

Abstract

Cancer is the major cause of morbidity and mortality in the world today. The third most common cancer and which is most diet related is colorectal cancer (CRC). Although there is complexity and limited understanding in the link between diet and CRC, the advancement in research methods have demonstrated the involvement of non-coding RNAs (ncRNAs) as key regulators of gene expression. MicroRNAs (miRNAs) which are a class of ncRNAs are key players in cancer related pathways in the context of dietary modulation. The involvement of ncRNA in cancer progression has recently been clarified throughout the last decade. ncRNAs are involved in biological processes relating to tumor onset and progression. The advances in research have given insights into cell to cell communication, by highlighting the pivotal involvement of extracellular vesicle (EV) associated-ncRNAs in tumorigenesis. The abundance and stability of EV associated ncRNAs act as a new diagnostic and therapeutic target for cancer. The understanding of the deranging of these molecules in cancer can give access to modulating the expression of the ncRNAs, thereby influencing the cancer phenotype. Food derived exosomes/vesicles (FDE) are gaining interest in the implication of exosomes in cell-cell communication with little or no understanding to date on the role FDE plays. There are resident microbiota in the colon; to which the imbalance in the normal intestinal occurrence leads to chronic inflammation and the production of carcinogenic metabolites that lead to neoplasm. Limited studies have shown the implication of various types of microbiome in CRC incidence, without particular emphasis on fungi and protozoa. This review discusses important dietary factors in relation to the expression of EV-associated ncRNAs in CRC, the impact of diet on the colon ecosystem with particular emphasis on molecular mechanisms of interactions in the ecosystem, the influence of homeostasis regulators such as glutathione, and its conjugating enzyme-glutathione S-transferase (GST) polymorphism on intestinal ecosystem, oxidative stress response, and its relationship to DNA adduct fighting enzyme-0-6-methylguanine-DNA methyltransferase. The understanding of the molecular mechanisms and interaction in the intestinal ecosystem will inform on the diagnostic, preventive and prognosis as well as treatment of CRC.

Growth Factors, PI3K/AKT/mTOR and MAPK Signaling Pathways in Colorectal Cancer Pathogenesis: Where Are We Now?

“…Cytochrome P450 enzymes activate these pro-carcinogens, which will be further converted in several metabolic pathways [ 31 ]. Moreover, N-nitroso compounds (NOC) obtained by the interaction between nitrogen oxides or nitrite with secondary amines and N-alkillamides have CRC carcinogenic properties [ 32 ]. In addition, the consumption of red meat and other animal products is conducive to trimethylamine N-oxide (TMAO) synthesis, a gut microbiota-derived metabolite of choline and L-carnitine, associated with an increased risk of CRC, cardiovascular disease, and diabetes.…”

Emerging Evidence on the Effects of Dietary Factors on the Gut Microbiome in Colorectal Cancer

“…Together with scaffolding protein FAM120A (family with sequence similarity 120A), IL13RA2 activation enhances the survival, invasion, migration, and dissemination of colon cancer ( 155 ). Exposure to different dietary constituents, varying pH as well as humid and stable temperature leads to heterogeneity of the oral cavity microbiota, of which certain organisms like Fusobacterium are highly implicated in the pathogenesis of CRC ( 156 , 157 ). F. nucleatum consistently increased the expression of miR21 in four colon cancer cell lines potentially via theTLR-4/MyD88/NF-κB signaling pathway.…”

Exploring the Inflammatory Pathogenesis of Colorectal Cancer

“…Although the specific mechanisms are not completely understood, given that GATA3 has been shown to be instrumental in T cell development, one potential explanation for this is that the decreased expression of GATA3 and decreased immunogenicity can increase CRC risk in the setting of unopposed inflammation caused by processed meats [ 42 ]. On the other hand, polyphenols, such as resveratrol and quercetin, found in wine, tea, coffee, vegetables and fruits, have some protective effects in tumor and oncogene suppression [ 43 ]. These influence pathways involved in microRNA, and TGF-beta1 transcription, and induce pathways with E2F3 and Sirt1 genes, which promote apoptosis in colonic cells [ 43 ].…”

“…On the other hand, polyphenols, such as resveratrol and quercetin, found in wine, tea, coffee, vegetables and fruits, have some protective effects in tumor and oncogene suppression [ 43 ]. These influence pathways involved in microRNA, and TGF-beta1 transcription, and induce pathways with E2F3 and Sirt1 genes, which promote apoptosis in colonic cells [ 43 ].…”