MIR210 as a potential molecular target to block invasion and metastasis of gastric cancer
MIR210 as a potential molecular target to block invasion and metastasis of gastric cancer
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DOI：
10.1016/j.mehy.2014.12.024
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发表时间：
2015-03-01
影响因子：
4.7
通讯作者：
Du, Yian
中科院分区：
文献类型：
--
作者：
Yu, Pengfei;Fan, Sunfu;Du, Yian
上皮间质转化（EMT）是胃癌侵袭、复发和转移的一个过程，EMT由肿瘤发生过程中出现的特定生理因素如缺氧触发。确定EMT的分子机制将有可能深入了解促进癌症复发和转移的途径，从而产生新的分子靶点，改善疾病的治疗。microRNA 210（MIR 210）是基于大量观察的在胃癌中介导EMT的候选分子。首先，MIR 210通常在胃癌中高度过表达。其次，MIR 210是一种低氧特异性miRNA，其表达在EMT发展的低氧环境中显著增加。第三，MIR 210受缺氧诱导因子1（HIF-1 α）调节，HIF-1 α是介导重要的肿瘤相关过程如肿瘤发生期间响应缺氧的EMT和血管生成的关键转录因子。最后，MIR 210与幽门螺杆菌感染有关，幽门螺杆菌感染通常在厌氧环境中发展，并且已知在胃癌的发展中具有因果作用。尽管研究表明MIR 210在胃癌中经常高表达，并与特定的病理状态相关，但尚未进行功能实验来确定MIR 210及其下游介质在胃癌发生和发展中的作用。在此，MIR 210被认为是治疗胃癌的可行的分子靶点，特别是用于抑制浸润和转移。(C)2015爱思唯尔有限公司版权所有。
The epithelial mesenchymal transition (EMT) is a process driving invasion, recurrence, and metastasis of gastric cancer, and EMT is triggered by specific physiological factors that arise during tumorigenesis, such as hypoxia. Identifying the molecular mechanisms underlying EMT will potentially yield insight into the pathways fueling cancer recurrence and metastasis and thus, lead to novel molecular targets that will improve treatment of the disease. The microRNA210 (MIR210) is such a candidate molecule mediating EMT in gastric cancer based on a number of observations. First, MIR210 is often highly overexpressed in gastric cancer. Second, MIR210 is a hypoxia-specific miRNA, and its expression is significantly increased in hypoxic environments where EMT develops. Third, MIR210 is regulated by hypoxia inducible factor 1 (HIF-1 alpha), a key transcription factor mediating important tumor associated processes such as EMT and angiogenesis in response to hypoxia during tumorigenesis. Finally, MIR210 has been intriguingly associated with Helicobacter pylori infection, which typically develops in an anaerobic environment and is known to have a causal role in the development of gastric cancer. Although studies have shown that MIR210 is often highly expressed in gastric cancer and associated with specific pathological conditions, functional experiments have not yet been performed to determine the role of MIR210 and downstream mediators in the development and progression of gastric cancer. Here, MIR210 is proposed as a viable molecular target in the treatment of gastric cancer, specifically for the inhibition of invasion and metastasis. (C) 2015 Elsevier Ltd. All rights reserved.