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Dysregulated Expression of miR-146a and Its Associated Immune Effectors in Peripheral Blood Mononuclear Cells of Esophageal Carcinoma Patients
Immunological Investigations ( IF 2.8 ) Pub Date : 2020-10-02 , DOI: 10.1080/08820139.2020.1828454
Ziba Nariman-Saleh-Fam 1, 2 , Yaser Mansoori 3 , Zahra Saadatian 4 , Javad Tavakkoly-Bazzaz 5 , Abdolreza Daraei 6 , Sepideh Zununi Vahed 7 , Habibollah Mahmoodzadeh 8 , Milad Bastami 2, 9
Affiliation  

ABSTRACT

Esophageal cancer is one of the least studied aggressive tumors, with the squamous cell carcinoma (ESCC) being the most frequent histological type around the world. Growing evidence has shown that the abnormal expression of microRNAs (miRNAs) in peripheral blood mononuclear cells (PBMCs) is closely related to the pathogenesis of cancers. MiR-146a is a crucial regulator of inflammatory cascades. There is currently no data available regarding the possible role of miR-146a in PBMCs of ESCC patients. We evaluated the expression of miR-146a, as well as its target genes (IRAK1 and TRAF6) and its associated immune effectors (NF-κB1, IL1B, and IL6) in PBMCs of 40 ESCC patients and 50 control subjects. The geometric mean expression of five transcripts was used for normalizing expressions. The PBMC level of miR-146a, as measured by RT-qPCR, was upregulated, whereas levels of its target genes, IRAK1 and TRAF6, were downregulated in ESCC patients. NF-κB1 and IL6 was downregulated in PBMCs of ESCC patients. There was no difference in terms of the IL1B level between patients and the control group. Logistic regression and receiver operating characteristic curve analysis suggested that a model with PBMC levels of either NF-κB1+ IL6 or NF-κB1+ miR-146a as predictors may discriminate ESCC patients from subjects of the control group. Our findings, in the context of the current literature, may suggest a possible downregulatory mechanism of immune responses in PBMCs of ESCC patients.



中文翻译:

食管癌患者外周血单个核细胞中miR-146a及其相关免疫效应子的异常表达

摘要

食管癌是研究最少的侵袭性肿瘤之一,鳞状细胞癌 (ESCC) 是世界上最常见的组织学类型。越来越多的证据表明,外周血单个核细胞(PBMCs)中microRNAs(miRNAs)的异常表达与癌症的发病机制密切相关。MiR-146a 是炎症级联反应的关键调节剂。目前没有关于 miR-146a 在 ESCC 患者 PBMC 中可能作用的数据。我们评估了 40 名 ESCC 患者和 50 名对照受试者的 PBMC 中 miR-146a 及其靶基因(IRAK1 和 TRAF6)及其相关免疫效应物(NF-κB1、IL1B 和 IL6)的表达。五个转录本的几何平均表达用于标准化表达。通过 RT-qPCR 测量的 miR-146a 的 PBMC 水平上调,而其靶基因 IRAK1 和 TRAF6 的水平在 ESCC 患者中下调。NF-κB1 和 IL6 在 ESCC 患者的 PBMC 中下调。患者和对照组之间的IL1B水平没有差异。Logistic 回归和受试者工作特征曲线分析表明,以 PBMC 水平的 NF-κB1+ IL6 或 NF-κB1+ miR-146a 作为预测因子的模型可以区分 ESCC 患者和对照组受试者。在当前文献的背景下,我们的研究结果可能表明 ESCC 患者 PBMC 中免疫反应的可能下调机制。患者和对照组之间的IL1B水平没有差异。Logistic 回归和受试者工作特征曲线分析表明,以 PBMC 水平的 NF-κB1+ IL6 或 NF-κB1+ miR-146a 作为预测因子的模型可以区分 ESCC 患者和对照组受试者。在当前文献的背景下,我们的研究结果可能表明 ESCC 患者 PBMC 中免疫反应的可能下调机制。患者和对照组之间的IL1B水平没有差异。Logistic 回归和受试者工作特征曲线分析表明,以 PBMC 水平的 NF-κB1+ IL6 或 NF-κB1+ miR-146a 作为预测因子的模型可以区分 ESCC 患者和对照组受试者。在当前文献的背景下,我们的研究结果可能表明 ESCC 患者 PBMC 中免疫反应的可能下调机制。

更新日期:2020-10-02
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