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miRNA 表达谱分析为胃癌相关免疫途径提供新的见解。

MicroRNA expression profiling provides novel insights into immune-related pathways involved in gastric cancer.

机构信息

Oncology Surgical Department, Sociedade Pernambucana de Combate ao Câncer - Hospital do Câncer de Pernambuco, Recife, Brazil.

Aggeu Magalhães Institute/Oswaldo Cruz Foundation, Recife, Brazil.

出版信息

Med Oncol. 2019 Aug 9;36(9):81. doi: 10.1007/s12032-019-1305-x.

DOI:10.1007/s12032-019-1305-x
PMID:31399867
Abstract

Gastric cancer is one of the most common cancers, and an increasing number of studies have found that microRNAs (miRNAs) play essential roles in gastric cancer progression; however, the roles of specific miRNAs involved in the immune response to this disease remain unclear. We compared the miRNA expression in tissues from primary gastric cancer patients and healthy controls to find miRNAs dysregulated in gastric cancer and used bioinformatics tools to determine potential roles of these miRNAs in the immune system. We evaluated 25 primary gastric cancer tissues and five healthy gastric tissues. Quantitative real-time polymerase chain reaction was performed for a set of miRNAs, followed by the prediction of their target genes and functional enrichment analysis of these targets. Analysis of a microarray dataset showed that the miRNA miR-196a-5p was significantly upregulated, while miR-374a-5p and miR-375 were downregulated in gastric cancer patients. In addition, miR-374-5p was significantly downregulated in patients with metastasis compared with its expression levels in non-metastatic patients (p = 0.03). Bioinformatics analysis suggested that the pathways regulated by these differentially expressed miRNAs were related to the immune response, cell adhesion, and cell migration. Most importantly, this study provides a new insight into the potential use of multiple miRNAs to find distinct pathways of immune regulation in gastric cancer.

摘要

胃癌是最常见的癌症之一,越来越多的研究发现 microRNAs(miRNAs)在胃癌进展中起着至关重要的作用;然而,特定 miRNAs 在这种疾病免疫反应中的作用仍不清楚。我们比较了原发性胃癌患者和健康对照者组织中的 miRNA 表达,以找到在胃癌中失调的 miRNAs,并使用生物信息学工具来确定这些 miRNAs 在免疫系统中的潜在作用。我们评估了 25 例原发性胃癌组织和 5 例健康胃组织。对一组 miRNA 进行了定量实时聚合酶链反应,随后对其靶基因进行预测,并对这些靶基因进行功能富集分析。微阵列数据集的分析表明,miR-196a-5p 在胃癌患者中显著上调,而 miR-374a-5p 和 miR-375 下调。此外,与非转移性患者相比,转移性患者的 miR-374-5p 表达水平显著下调(p=0.03)。生物信息学分析表明,这些差异表达的 miRNAs 调控的途径与免疫反应、细胞黏附和细胞迁移有关。最重要的是,这项研究为利用多种 miRNAs 寻找胃癌免疫调节的独特途径提供了新的见解。

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本文引用的文献

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Clinical efficacy of immune checkpoint inhibitors in the treatment of unresectable advanced or recurrent gastric cancer: an evidence-based review of therapies.免疫检查点抑制剂治疗不可切除的晚期或复发性胃癌的临床疗效:基于证据的治疗综述
Onco Targets Ther. 2018 Nov 21;11:8239-8250. doi: 10.2147/OTT.S152514. eCollection 2018.
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关于检查点阻断的关键问题——微小RNA是答案吗?
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PD-1 and PD-L1 Up-regulation Promotes T-cell Apoptosis in Gastric Adenocarcinoma.PD-1和PD-L1上调促进胃腺癌中的T细胞凋亡。
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Could OX40 agonist antibody promote activation of the anti-tumor immune response in gastric cancer?OX40激动剂抗体能否促进胃癌中抗肿瘤免疫反应的激活?
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MicroRNA-335-5p is a potential suppressor of metastasis and invasion in gastric cancer.微小 RNA-335-5p 是胃癌转移和侵袭的潜在抑制因子。
Clin Epigenetics. 2017 Oct 17;9:114. doi: 10.1186/s13148-017-0413-8. eCollection 2017.
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