MUC13, a transmembrane mucin glycoprotein, is overexpressed in colorectal cancer (CRC), however, its regulation and functions are not fully understood. It has been shown that MUC13 protects colonic epithelial cells from apoptosis. Therefore, studying MUC13 and MUC13-regulated pathways may reveal promising therapeutic approaches for CRC treatment. Growing evidence suggests that microRNAs (miRs) are involved in the development and progression of CRC. In the present study, the MUC13-miR-4647 axis was addressed in association with survival of patients. miR-4647 is predicted in silico to bind to the MUC13 gene and was analyzed by RT-qPCR in 187 tumors and their adjacent non-malignant mucosa of patients with CRC. The impact of previously mentioned genes on survival and migration abilities of cancer cells was validated in vitro. Significantly upregulated MUC13 (P=0.02) in was observed tumor tissues compared with non-malignant adjacent mucosa, while miR-4647 (P=0.05) showed an opposite trend. Higher expression levels of MUC13 (log-rank P=0.05) were associated with worse patient's survival. The ectopic overexpression of studied miR resulted in decreased migratory abilities and worse survival of cells. Attenuated MUC13 expression levels confirmed the suppression of colony forming of CRC cells. In summary, the present data suggested the essential role of MUC13-miR-4647 in patients' survival, and this axis may serve as a novel therapeutic target. It is anticipated MUC13 may hold significant potential in the screening, diagnosis and treatment of CRC.

• Keywords
• MUC13, colorectal cancer risk and clinical outcomes, microRNA, translation research,
• Publication type
• Journal Article MeSH

Genetic variations in miRNAs binding site might participate in cancer risk. This study aimed to systematically review the association between miRNA-binding site polymorphisms and colorectal cancer (CRC). Electronic literature search was carried out on PubMed, Web of Science (WOS), Scopus, and Embase. All types of observational studies till 30 November 2018 were included. Overall 85 studies (21 SNPs) from two systematic searches were included analysis. The results showed that in the Middle East population, the minor allele of rs731236 was associated with decreased risk of CRC (heterozygote model: 0.76 [0.61-0.95]). The minor allele of rs3025039 was related to increased risk of CRC in East Asian population (allelic model: 1.25 [1.01-1.54]). Results for rs3212986 were significant in overall and subgroup analysis (P < .05). For rs1801157 in subgroup analysis the association was significant in Asian populations (including allelic model: 2.28 [1.11-4.69]). For rs712, subgroup analysis revealed a significant (allelic model: 1.41 [1.23-1.61]) and borderline (allelic model: 0.92 [0.84-1.00]) association in Chinese and Czech populations, respectively. The minor allele of rs17281995 increased risk of CRC in different genetic models (P < .05). Finally, rs5275, rs4648298, and rs61764370 did not show significant associations. In conclusion, minor allele of rs3025039, rs3212986, and rs712 polymorphisms increases the risk of CRC in the East Asian population, and heterozygote model of rs731236 polymorphism shows protective effect in the Middle East population. In Europeans, the minor allele of rs17281995 may increase the risk of CRC, while rs712 may have a protective effect. Further analysis based on population stratifications should be considered in future studies.

• Keywords
• colorectal cancer, meta-analysis, microRNAs, polymorphism,
• MeSH
• 3' Untranslated Regions genetics   MeSH
• Alleles MeSH
• Asian People genetics   MeSH
• Genetic Predisposition to Disease * MeSH
• Polymorphism, Single Nucleotide MeSH
• Colorectal Neoplasms epidemiology   genetics   MeSH
• Humans MeSH
• MicroRNAs metabolism   MeSH
• Observational Studies as Topic MeSH
• Gene Expression Regulation, Neoplastic MeSH
• Risk Factors MeSH
• Binding Sites genetics   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Meta-Analysis MeSH
• Research Support, Non-U.S. Gov't MeSH
• Systematic Review MeSH
• Geographicals
• Czech Republic epidemiology   MeSH
• Asia, Eastern epidemiology   MeSH
• Middle East epidemiology   MeSH
• Names of Substances
• 3' Untranslated Regions MeSH
• MicroRNAs MeSH

Mucins and their glycosylation have been suggested to play an important role in colorectal carcinogenesis. We examined potentially functional genetic variants in the mucin genes or genes involved in their glycosylation with respect to colorectal cancer (CRC) risk and clinical outcome. We genotyped 23 single nucleotide polymorphisms (SNPs) covering 123 SNPs through pairwise linkage disequilibrium (r2>0.80) in the MUC1, MUC2, MUC4, MUC5AC, MUC6, and B3GNT6 genes in a hospital-based case-control study of 1532 CRC cases and 1108 healthy controls from the Czech Republic. We also analyzed these SNPs in relation to overall survival and event-free survival in a subgroup of 672 patients. Among patients without distant metastasis at the time of diagnosis, two MUC4 SNPs, rs3107764 and rs842225, showed association with overall survival (HR 1.40, 95%CI 1.08-1.82, additive model, log-rank p = 0.004 and HR 0.64, 95%CI 0.42-0.99, recessive model, log-rank p = 0.01, respectively) and event-free survival (HR 1.31, 95%CI 1.03-1.68, log-rank p = 0.004 and HR 0.64, 95%CI 0.42-0.96, log-rank p = 0.006, respectively) after adjustment for age, sex and TNM stage. Our data suggest that genetic variation especially in the transmembrane mucin gene MUC4 may play a role in the survival of CRC and further studies are warranted.

• MeSH
• Progression-Free Survival MeSH
• Adult MeSH
• Genotype MeSH
• Glycosylation MeSH
• Polymorphism, Single Nucleotide genetics   MeSH
• Kaplan-Meier Estimate MeSH
• Colorectal Neoplasms genetics   mortality   pathology   MeSH
• Middle Aged MeSH
• Humans MeSH
• Mucin-4 genetics   metabolism   MeSH
• Mucins genetics   metabolism   MeSH
• Biomarkers, Tumor genetics   MeSH
• Colonic Neoplasms genetics   mortality   pathology   MeSH
• Disease-Free Survival MeSH
• Risk Factors MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Case-Control Studies MeSH
• Linkage Disequilibrium MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Geographicals
• Czech Republic MeSH
• Names of Substances
• MUC4 protein, human MeSH Browser
• Mucin-4 MeSH
• Mucins MeSH
• Biomarkers, Tumor MeSH

DNA repair processes are involved in both the onset and treatment efficacy of colorectal cancer (CRC). A change of a single nucleotide causing an amino acid substitution in the corresponding protein may alter the efficiency of DNA repair, thus modifying the CRC susceptibility and clinical outcome. We performed a candidate gene approach in order to analyze the association of non-synonymous single nucleotide polymorphisms (nsSNPs) in the genes covering the main DNA repair pathways with CRC risk and clinical outcome modifications. Our candidate polymorphisms were selected according to the foremost genomic and functional prediction databases. Sixteen nsSNPs in 12 DNA repair genes were evaluated in cohorts from the Czech Republic and Austria. Apart from the tumor-node-metastasis (TNM) stage, which occurred as the main prognostic factor in all of the performed analyses, we observed several significant associations of different nsSNPs with survival and clinical outcomes in both cohorts. However, only some of the genes (REV3L, POLQ, and NEIL3) were prominently defined as prediction factors in the classification and regression tree analysis; therefore, the study suggests their association for patient survival. In summary, we provide observational and bioinformatics evidence that even subtle alterations in specific proteins of the DNA repair pathways may contribute to CRC susceptibility and clinical outcome.

• Keywords
• DNA repair genes, colorectal cancer susceptibility, functional single nucleotide polymorphism, survival analysis,
• MeSH
• Survival Analysis MeSH
• DNA-Binding Proteins genetics   MeSH
• DNA-Directed DNA Polymerase genetics   MeSH
• DNA Polymerase theta MeSH
• Adult MeSH
• Genetic Predisposition to Disease MeSH
• Polymorphism, Single Nucleotide MeSH
• Cohort Studies MeSH
• Colorectal Neoplasms genetics   mortality   pathology   MeSH
• Middle Aged MeSH
• Humans MeSH
• Neoplasm Metastasis MeSH
• N-Glycosyl Hydrolases genetics   MeSH
• Odds Ratio MeSH
• DNA Repair genetics   MeSH
• Disease-Free Survival MeSH
• Aged MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Geographicals
• Czech Republic MeSH
• Austria MeSH
• Names of Substances
• DNA-Binding Proteins MeSH
• DNA-Directed DNA Polymerase MeSH
• N-Glycosyl Hydrolases MeSH
• NEIL3 protein, human MeSH Browser
• REV3L protein, human MeSH Browser

AIM: The objective of this work was to test the effects of adding dried Chicory root and White lupine food on small bowel morphology and compare it to a standard commercial diet. BACKGROUND: Various commercial gluten-free products, gluten-free raw materials and gluten-free plants are this time available on the food market, but there are still not enough information about their effect on the small bowel morphology. METHODS: Altogether thirty rabbits were used in this study. The control diet (C) contained common feed components. The first experimental diet (E1) contained (per kg) 60 g of dried chicory roots instead of barley, whereas the second experimental diet (E2) was based on white lupine seeds (cv. Amiga; 120 g per kg diet) instead of the soybean meal used in the control diet. The experiment started when the rabbits were 34-days old and lasted until they were 55-days old. At the end, one jejunal small bowel tissue was sampled, and both the heights and depths of the villi and crypts were measured. RESULTS: The highest villi were measured in the E1 (598.99 µm) group, mean in the C (590.30 µm) group and the lowest were in the E2 (563.74 µm) group. The most intense mucin villous positivity was observed in the E2 group, followed by the E1 group, and the weakest positivity was found in the visible C group. CONCLUSION: Chicory root has practical uses in gluten-free industries.

• Keywords
• Celiac disease, Gluten-free diet, Nutrition, Small bowel, Villi intestinalis,
• Publication type
• Journal Article MeSH