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| 1 | Relationship between Fusobacterium nucleatum,inflammatory mediators and microRNAs in colorectal carcinogenesis显示文摘AIM To examine the effect of Fusobacterium nucleatum(F. nucleatum) on the microenvironment of colonic neoplasms and the expression of inflammatory mediators and microRNAs(miRNAs).METHODS Levels of F. nucleatum DNA, cytokine gene mRNA(TLR2, TLR4, NFKB1, TNF, IL1 B, IL6 and IL8), and potentially interacting miRNAs(miR-21-3p, miR-22-3p, mi R-28-5p, miR-34a-5p, miR-135b-5p) were measured by quantitative polymerase chain reaction(qPCR) TaqMan? assays in DNA and/or RNA extracted from the disease and adjacent normal fresh tissues of 27 colorectal adenoma(CRA) and 43 colorectal cancer(CRC) patients. KRAS mutations were detected by direct sequencing and microsatellite instability(MSI) status by multiplex PCR. Cytoscape v3.1.1 was used to construct the postulated miRNA:mRNA interaction network.RESULTS Overabundance of F. nucleatum in neoplastic tissue compared to matched normal tissue was detected in CRA(51.8%) and more markedly in CRC(72.1%). We observed significantly greater expression of TLR4, IL1 B, IL8, and miR-135 b in CRA lesions and TLR2, IL1 B, IL6, IL8, mi R-34 a and miR-135 b in CRC tumours compared to their respective normal tissues. Only two transcripts for miR-22 and miR-28 were exclusively downregulated in CRC tumour samples. The mRNA expression of IL1 B, IL6, IL8 and miR-22 was positively correlated with F. nucleatum quantification in CRC tumours. The mRNA expression of miR-135 b and TNF was inversely correlated. The miRNA:mRNA interaction network suggested that the upregulation of miR-34 a in CRC proceeds via a TLR2/TLR4-dependent response to F. nucleatum. Finally, KRAS mutations were more frequently observed in CRC samples infected with F. nucleatum and were associated with greater expression of miR-21 in CRA, while IL8 was upregulated in MSI-high CRC.CONCLUSION Our findings indicate that F. nucleatum is a risk factor for CRC by increasing the expression of inflammatory mediators through a possible mi RNA-mediated activation of TLR2/TLR4. | Marcela Alcantara Proenca Joice Matos Biselli Maysa Succi Fábio Eduardo Severino Gustavo Noriz Berardinelli Alaor Caetano Rui Manuel Reis David J Hughes Ana Elizabete Silva | 2018 | World Journal of Gastroenterology2018，24，47： | 15 |
| 2 | Therapeutic drug monitoring of racemic citalopram: a 5-year experience in Sweden, 1992-1997显示文摘 | REIS M LUNDMARK J BENGTSSON F | 2003 | Ther Drug Monit2003，25，2： | 1 |
| 3 | Dexmedetomidine: current role in anesthesia and intensive care显示文摘 | Afonso J Reis F | 2012 | Rev Bras Anestesiol2012，62，： | 1 |
| 4 | Dexmedetomidine:current role in anes- thesia and intensive care 显示文摘 | Afonso J Reis F | 2012 | Rev Bras Anestesiol2012，62，1： | 1 |
| 5 | Vapor Bubble Departure in Forced Convection Boiling显示文摘 | Rei R Bernhard D M | 1993 | Int J Heat and Mass Transfer1993，36，： | 1 |
| 6 | Topiramate selectively decreases intracortical excitability in human motor cortex 显示文摘 | Reis J Tergau F Hamer HM | 2002 | Epilepsia2002，43，： | 1 |
| 7 | Dexamethasone-loaded scaffolds prepared by supercritical-assisted phase inversion显示文摘 | Duarte A R C Mano J F Reis R L | 2009 | Acta Biomaterialia2009，5，6： | 1 |
| 8 | Osteochondral defects: Present situation and tissue engineering approaehes显示文摘 | MANO J F REIS R L | 2007 | Journal of Tissue Engineering and Regenerative Medicine2007，1，4： | 1 |
| 9 | Estimation Performance and Strategies Use of Mexican 5^th and 8^th Grade Student Sample 显示文摘 | Reys R E Reys B J Alfinio F P | 1991 | Educational Students in Mathematics1991，22，4： | 1 |
| 10 | Dexmedetomidine: eurrent role in anesthe- siaand intensive care显示文摘 | Fonso J Reis F | 2012 | Rev Bras Anestesiol2012，62，1： | 1 |
| 11 | The Clinical and Topographic Spectrum of Cerebellar Infarcts:a Clinical-Magnetic Resonance Imaging Correlation Study 显示文摘 | Barth A Bogousslavsky J Rei F | 1993 | Ann Neurol ( S0364 - 5134 )1993，33，： | 1 |
| 12 | Dexmedetomidine: current role in anesthesia and intensive care显示文摘 | Atbnso J Reis F | 2012 | Rev Bras Anestesiol2012，62，1： | 1 |
| 13 | Numerical simulation of the impact of liquid droplet on porous surfaces 显示文摘 | REIS J N GRIFFITBS R F SANTOS J M | 2004 | Journal of Computational Physics2004，198，2： | 1 |
| 14 | Dexmedetomidine: current role in anesthesia and intensive care显示文摘 | Afonso J Reis F | 2012 | Rev Bras Anesthesiol2012，62，1： | 1 |
| 15 | Team - based learning during clerkships: a cohort study显示文摘 | Figueiro - Filho EA dos Reis F J Goncalves LM | 2015 | Med Edue2015，49，11： | 1 |
| 16 | Correlates of physical activity:Why are some people physically active and others not?显示文摘 | Bauman A E Reis R S Sallis J F | 2012 | Lancet2012，380，： | 1 |
| 17 | Dexmedetomidine:current role in anesthesia and intensive care显示文摘 | Afonso J Reis F | 2012 | Rev Bras Anestesiol2012，62，1： | 1 |
| 18 | Dexmedetomidine: current role in anesthesia and intensive care 显示文摘 | Afonso J Reis F | 2012 | Rev Bras Anestesiol2012，62，1： | 1 |
| 19 | Serum concentrations of fluoxetine in the clinical treatment setting显示文摘 | Lundmark J Reis M Bengtsson F | 2001 | Therap Drug Monit2001，23，2： | 1 |
| 20 | Dexmedetomidine:Current Role in Anesthesia and Intensive Care显示文摘 | Afonso J Reis F | 2012 | Rev Bras Anestesiol2012，62，1： | 1 |
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