Details

Autor(en) / Beteiligte

• Proença, Marcela Alcântara
• Biselli, Joice Matos
• Succi, Maysa
• Severino, Fábio Eduardo
• Berardinelli, Gustavo Noriz
• Caetano, Alaor
• Reis, R. M.
• Hughes, David J.
• Silva, Ana Elizabete

Titel

Relationship between Fusobacterium nucleatum, inflammatory mediators and microRNAs in colorectal carcinogenesis

Ist Teil von

• World journal of gastroenterology : WJG, 2018-12, Vol.24 (47), p.5351-5365

Ort / Verlag

United States: Baishideng Publishing Group

Erscheinungsjahr

2018

Quelle

EZB Electronic Journals Library

Beschreibungen/Notizen

• 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, IL1B, IL6 and IL8), and potentially interacting miRNAs (miR-21-3p, miR-22-3p, miR-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, IL1B, IL8, and miR-135b in CRA lesions and TLR2, IL1B, IL6, IL8, miR-34a and miR-135b 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 IL1B, IL6, IL8 and miR-22 was positively correlated with F. nucleatum quantification in CRC tumours. The mRNA expression of miR-135b and TNF was inversely correlated. The miRNA:mRNA interaction network suggested that the upregulation of miR-34a 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 miRNA-mediated activation of TLR2/TLR4 We thank Lucas Trevizani Rasmussen for kindly donating some miRNA probes. We are grateful to the São Paulo Research Foundation (FAPESP, NO. 2015/21464-0) for the support for English revision, the Coordination for the Improvement of Higher Education Personnel (CAPES) for the doctoral scholarship, and the National Council for Scientific and Technological Development (CNPq, NO. 310120/2015-2) for the productivity research scholarship.