Downregulation of miR-186 is associated with metastatic recurrence of gastrointestinal stromal tumors.

Downregulation of miR-186 is associated with metastatic recurrence of gastrointestinal stromal tumors.
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DOI:
10.3892/ol.2017.6911
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发表时间:
2017-11
期刊:
影响因子:
2.9
通讯作者:
Suzuki H
Suzuki H
中科院分区:
医学4区
文献类型:
--
作者:
Niinuma T;Kai M;Kitajima H;Yamamoto E;Harada T;Maruyama R;Nobuoka T;Nishida T;Kanda T;Hasegawa T;Tokino T;Sugai T;Shinomura Y;Nakase H;Suzuki H

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虽然microRNAs调节失调(miRNAs/miRs)是人类恶性肿瘤的共同特征,但它与胃肠道间质瘤(GIST)的关系尚不完全清楚。本研究旨在确定在胃肠道间质瘤转移中起作用的miRNAs。使用微阵列分析了一系列32例原发GIST的miRNA表达谱,发现miR-186在转移复发的肿瘤中下调。对100例原发GIST的独立队列进行的逆转录定量聚合酶链式反应分析显示,miR-186低表达与转移复发和预后不良有关。在GIST-T1细胞中抑制miR-186可促进细胞迁移。基因表达芯片分析显示,miR-186抑制上调了一系列与肿瘤转移有关的基因,包括胰岛素样生长因子结合蛋白3、AKT丝氨酸/苏氨酸激酶2、肝细胞生长因子受体、CXC趋化因子受体4和含有表皮生长因子的纤维蛋白样胞外基质蛋白1。这些结果表明miR-186表达下调参与了GIST的转移复发,miR-186水平可能是临床预后的预测生物标志物。
Although dysregulation of microRNAs (miRNAs/miRs) is a common feature of human malignancies, its involvement in gastrointestinal stromal tumors (GISTs) is not fully understood. The present study aimed to identify the miRNAs that perform a role in GIST metastasis. miRNA expression profiles from a series of 32 primary GISTs were analyzed using microarrays, and miR-186 was observed to be downregulated in tumors exhibiting metastatic recurrence. Reverse transcription-quantitative polymerase chain reaction analysis of an independent cohort of 100 primary GISTs revealed that low miR-186 expression is associated with metastatic recurrence and a poor prognosis. Inhibition of miR-186 in GIST-T1 cells promoted cell migration. Gene expression microarray analysis demonstrated that miR-186 inhibition upregulated a set of genes implicated in cancer metastasis, including insulin-like growth factor-binding protein 3, AKT serine/threonine kinase 2, hepatocyte growth factor receptor, CXC chemokine receptor 4 and epidermal growth factor-containing fibulin-like extracellular matrix protein 1. These results suggest that the downregulation of miR-186 is involved in the metastatic recurrence of GISTs, and that miR-186 levels could potentially be a predictive biomarker for clinical outcome.
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