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miR-584 在原发性和高级别胃癌中的表达波动。

Fluctuating expression of miR-584 in primary and high-grade gastric cancer.

机构信息

Department of Biology, Tehran-east Payame Noor University, Tehran, Iran.

Department of Cell and Molecular Biology and Microbiology, Faculty of Biological Science and Technology, University of Isfahan, Isfahan, Iran.

出版信息

BMC Cancer. 2020 Jul 2;20(1):621. doi: 10.1186/s12885-020-07116-5.

DOI:10.1186/s12885-020-07116-5
PMID:32615958
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7345521/
Abstract

BACKGROUND

Gastric cancer is the fifth most common cancer worldwide. Along with environmental factors, such as Helicobacter pylori (H. pylori) infection, genetic changes play important roles in gastric tumor formations. miR-584 is a less well-characterized microRNA (miRNA), with apparent activity in human cancers. However, miR-584 expression pattern in gastric cancer development has remained unclear. This study aims to analyze the expression of miR-584 in gastric cancer samples and investigates the associations between this miRNA and H. pylori infection and clinical characteristics.

METHODS

The expression level of miR-584 was studied in primary gastric cancers versus healthy control gastric mucosa samples using the RT-qPCR method. The clinical data were analyzed statistically in terms of miR-584 expression. In silico studies were employed to study miR-584 more broadly in order to assess its expression and find new potential target genes.

RESULTS

Both experimental and in silico studies showed up-regulation of miR-584 in patients with gastric cancer. This up-regulation seems to be induced by H. pylori infection since the infected samples showed increased levels of miR-584 expression. Deeper analyses revealed that miR-584 undergoes a dramatic down-regulation in late stages, invasive and lymph node-metastatic gastric tumors. Bioinformatics studies demonstrated that miR-584 has a substantial role in cancer pathways and has the potential to target STAT1 transcripts. Consistent with the inverse correlation between TCGA RNA-seq data of miR-584 and STAT1 transcripts, the qPCR analysis showed a significant negative correlation between these two RNAs in a set of clinical samples.

CONCLUSION

miR-584 undergoes up-regulation in the stage of primary tumor formation; however, becomes down-regulated upon the progression of gastric cancer. These findings suggest the potential of miR-584 as a diagnostic or prognostic biomarker in gastric cancer.

摘要

背景

胃癌是全球第五大常见癌症。除了环境因素,如幽门螺杆菌(H. pylori)感染,遗传变化在胃肿瘤形成中也起着重要作用。miR-584 是一种研究较少的 microRNA(miRNA),在人类癌症中具有明显的活性。然而,miR-584 在胃癌发展中的表达模式仍不清楚。本研究旨在分析胃癌组织中 miR-584 的表达,并研究该 miRNA 与 H. pylori 感染和临床特征之间的关系。

方法

采用 RT-qPCR 方法检测原发性胃癌与健康对照胃黏膜组织中 miR-584 的表达水平。根据 miR-584 的表达情况对临床资料进行统计学分析。通过计算机模拟研究进一步研究 miR-584,以评估其表达并寻找新的潜在靶基因。

结果

实验和计算机模拟研究均显示胃癌患者 miR-584 表达上调。这种上调似乎是由 H. pylori 感染诱导的,因为感染样本显示 miR-584 表达水平升高。进一步分析表明,miR-584 在晚期、侵袭性和淋巴结转移性胃癌中显著下调。生物信息学研究表明,miR-584 在癌症途径中具有重要作用,并具有靶向 STAT1 转录本的潜力。与 TCGA RNA-seq 数据中 miR-584 和 STAT1 转录本之间的负相关一致,qPCR 分析显示在一组临床样本中这两种 RNA 之间存在显著的负相关。

结论

miR-584 在原发性肿瘤形成阶段上调,但在胃癌进展过程中下调。这些发现表明 miR-584 可能成为胃癌的诊断或预后生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2143/7345521/10deeb63ea67/12885_2020_7116_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2143/7345521/f67e85ec7bc7/12885_2020_7116_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2143/7345521/442c8747d205/12885_2020_7116_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2143/7345521/59fd5e0b9c59/12885_2020_7116_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2143/7345521/eafa926281e0/12885_2020_7116_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2143/7345521/10deeb63ea67/12885_2020_7116_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2143/7345521/f67e85ec7bc7/12885_2020_7116_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2143/7345521/442c8747d205/12885_2020_7116_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2143/7345521/59fd5e0b9c59/12885_2020_7116_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2143/7345521/eafa926281e0/12885_2020_7116_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2143/7345521/10deeb63ea67/12885_2020_7116_Fig5_HTML.jpg

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