Department of Biology, UNESP, Univ. Estadual Paulista, Campus of São José do Rio Preto, São José do Rio Preto, São Paulo 15054-000, Brazil.
Department of Surgery and Orthopedics, Faculty of Medicine, UNESP, Univ. Estadual Paulista, Campus of Botucatu, Botucatu, São Paulo 18618-687, Brazil.
World J Gastroenterol. 2018 Dec 21;24(47):5351-5365. doi: 10.3748/wjg.v24.i47.5351.
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 /.
研究（）对结肠肿瘤微环境及炎症介质和 microRNAs（miRNAs）表达的影响。
采用定量聚合酶链反应（qPCR）TaqMan 检测 27 例结直肠腺瘤（CRA）和 43 例结直肠癌（CRC）患者肿瘤及相应正常组织中 DNA 及细胞因子基因 mRNA（、、、、、）和可能相互作用的 miRNAs（miR-21-3p、miR-22-3p、miR-28-5p、miR-34a-5p、miR-135b-5p）水平。采用直接测序法检测 突变，多重 PCR 法检测微卫星不稳定性（MSI）状态。采用 Cytoscape v3.1.1 构建假定的 miRNA：mRNA 相互作用网络。
与 CRA （51.8%）相比，CRC （72.1%）肿瘤组织中 过度表达。与相应正常组织相比，我们发现 CRA 病变组织中 miR-21、miR-22、miR-28 和 miR-135b 表达显著增加，CRC 肿瘤组织中 、 、 、miR-34a 和 miR-135b 表达显著增加。CRC 肿瘤样本中仅两个 miR-22 和 miR-28 转录本下调。CRC 肿瘤组织中 miR-135b 和 的表达与 定量呈负相关。miRNA：mRNA 相互作用网络表明，CRC 中 miR-34a 的上调是通过对 的 /-依赖性反应而发生的。最后，CRC 样本中 突变较易发生在感染 的样本中，与 CRA 中 miR-21 表达增加有关，而 MSI-高 CRC 中 上调。
我们的研究结果表明，通过可能通过 miRNA 介导的 / 激活增加炎症介质的表达，成为 CRC 的危险因素。
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