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Proença, Marcela Alcântara; Biselli, Joice Matos; Succi, Maysa; Severino, Fábio Eduardo; Berardinelli, Gustavo Noriz; Caetano, Alaor; Reis, Rui Manuel; Hughes, David J; Silva, Ana Elizabete
World journal of gastroenterology : WJG, 2018-Dec-21, 2018-12-21, 20181221, Volume: 24, Issue: 47Journal Article
To examine the effect of ( ) on the microenvironment of colonic neoplasms and the expression of inflammatory mediators and microRNAs (miRNAs). Levels of DNA, cytokine gene mRNA ( , , , , , and ), 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. 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. Overabundance of 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 , , , and miR-135b in CRA lesions and , , , , 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 , , and miR-22 was positively correlated with quantification in CRC tumours. The mRNA expression of miR-135b and was inversely correlated. The miRNA:mRNA interaction network suggested that the upregulation of miR-34a in CRC proceeds a / -dependent response to . Finally, mutations were more frequently observed in CRC samples infected with and were associated with greater expression of miR-21 in CRA, while was upregulated in MSI-high CRC. Our findings indicate that is a risk factor for CRC by increasing the expression of inflammatory mediators through a possible miRNA-mediated activation of / .
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