Colorectal cancer: The epigenetic role of microbiome

Table 1 Gut microbiota are involved in CRC carcinogenesis

Microorganism	Role in CRC initiation/progression	Ref.
Lactobacillus casei BL23	Immunomodulatory effect via downregulation of the IL-22, and an antiproliferative effect, via upregulation of caspase-7 and caspase-9	[109]
Escherichia coli NC101	Production of colibactin that induces CRC	[110]
Fusobacterium nucleatum	Activation of β-catenin signaling and induction of oncogenic gene expression that promotes growth of CRC cells via the FadA adhesion virulence facto. It produces also the autotransporter protein, Fap2, that has been shown to potentiate the progress of CRC via inhibiting immune cell activity	[111]
Eubacterium rectale	Production of butyrate to induce IL-10, the anti-inflammatory cytokine	[112]
Bacteroides fragilis	Production of Enterotoxigenic Bacteroides fragilis (ETBF) toxin that promotes CRC by modulating the mucosal immune response and inducing epithelial cell changes. ETBF stimulates E-cadherin cleavage and facilitates cell tumor metastasis	[113]
Streptococcus bovis	Triggering of inflammations, bacteremia, and endocarditis, that leads ultimately to colorectal cancer	[114]
Clostridium septicum	Production of alpha toxin that binds GPI-anchored cell surface receptors including the human folate receptor as well as the neuronal molecules contactin and Thy-1 (CD90)	[115]
Enterococcus faecalis	Damaging the colonic epithelial cell DNA	[116]
Bifidobacterium	Production of β-galactosidases, which has antitumor activity	[117]
Helicobacter pylori	Induction of inflammatory responses, alteration of gut microflora and release of gastrin, which may contribute to tumor formation	[118]
Faecalibacterium prausnitzii	Production of butyrate to induce IL-10, the anti-inflammatory cytokine that protects against cancer formation	[119]
Enterotoxigenic bacteroides	Induction of early-stage carcinogenic, that might lead to early colorectal carcinogenesis	[113]
Clostridium nexile	Contribution to the anticancer effect of Pseudomonas aeruginosa. It improves also malnutrition in infants	[120]
Fusobacterium varium	Activate the E-cadherin/β-catenin signaling pathway and association with epigenetic phenotype, such as microsatellite instability and hypermethylation, via its strong adhesive and invasive abilities resulting in malignant transformation of epithelial cells	[121]
Actinomyces odontolyticus	Causes colon actinomycosis only when the epithelial barrier was perished	[122]
Veillonella dispar	Might be able to enhance the dosage response to CRC chemotherapeutic agents or reduce the side effects of these drugs	[123]

CRC: Colorectal cancer; ETBF: Enterotoxigenic Bacteroides fragilis.

Table 2 A list of representative miRNAs identified in tumor tissues that are of prognostic value in CRC patients

miRNA	Role in CRC	Ref.
miR-15a/miR-16	Their low expression levels were associated with poor disease-free survival and overall survival	[124]
miR-17-5p	Its high expression was associated with disease-free survival	[125]
miR-21	Its high level of expression was associated with poor survival and poor therapeutic outcomes	[126]
miR-29a	Its elevated level of expression was associated with a longer disease-free survival in stage II CRC patients	[127]
miR-34a-5p	Its high expression was correlated with disease-free survival	[128]
miR-106a	Its downregulation was associated with shortened overall survival	[125]
miR-132	Its decreased expression level was associated with poorer overall survival and occurrence of distant metastasis especially in liver	[129]
miR-150	Its elevated expression level was associated with longer overall survival. While its low level of expression was associated with poor therapeutic outcome in patients treated with 5-Fluro uracil	[130]
miR-195	Its low expression rate was associated with occurrence of lymph node metastasis and advanced tumor grade/stage	[131]
miR-199b	Increased in metastatic CRC tissue compared with non-metastatic CRC tissue. Furthermore, its low expression was associated with longer overall survival	[132]
miR-203	Its elevated expression level was associated with advanced TNM staging and poorer overall survival	[130]
miR-320e	Its high expression was associated with poorer overall survival in stage III colon cancer patients	[133]
miR-429	Its overexpression was associated with overall survival; low level of expression was associated with response to 5-Fluro uracil-based chemotherapy	[134]
miR-494	Its elevated expression was associated with shorter DFS and overall survival	[135]
miR-625-3p	High expressions were associated with higher overall survival and enhanced response to therapy	[136]

CRC: Colorectal cancer.