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微小RNA介导的基质金属蛋白酶调节在恶性肿瘤治疗与诊断中的作用

Role of microRNA-mediated MMP regulation in the treatment and diagnosis of malignant tumors.

作者信息

Li Liqin, Li Heng

机构信息

Huzhou Key Laboratory of Molecular Medicine; Huzhou Central Hospital; Huzhou, China.

The First Affiliated Hospital of Huzhou Teachers College; The First People's Hospital of Huzhou; Huzhou, China.

出版信息

Cancer Biol Ther. 2013 Sep;14(9):796-805. doi: 10.4161/cbt.25936. Epub 2013 Aug 5.

Abstract

Matrix metalloproteinases (MMPs) play important roles in tumor cell proliferation and apoptosis and contribute to tumor growth, angiogenesis, migration, and invasion primarily via extracellular matrix (ECM) degradation and/or the activation of pre-pro-growth factors. Recently, there has been considerable interest in the posttranscriptional regulation of MMPs via microRNAs (miRs). In this review, we highlight the complicated interactive network comprised of different MMPs and their regulating microRNAs, as well as the ways in which these interactions influence cancer development, including tumor angiogenesis, growth, invasion, and metastasis. Based on the conclusive roles that microRNAs play in the regulation of MMPs during cancer progression, we discuss the potential use of microRNA-mediated MMP regulation in the diagnosis and treatment of tumors from the clinical perspective. In particular, microRNA-mediated MMP regulation may lead to the development of promising new MMP inhibitors that target MMPs more selectively, and this approach may also target multiple molecules in a network, leading to the efficient regulation of distinct biological processes relevant to malignant tumors. A thorough understanding of the mechanisms underlying microRNA-mediated MMP regulation during tumor progression will help to provide new insights into the diagnosis and treatment of malignant tumors.

摘要

基质金属蛋白酶(MMPs)在肿瘤细胞增殖和凋亡中发挥重要作用,主要通过细胞外基质(ECM)降解和/或前体生长因子的激活,促进肿瘤生长、血管生成、迁移和侵袭。最近,通过微小RNA(miRs)对MMPs进行转录后调控引起了广泛关注。在本综述中,我们重点介绍了由不同MMPs及其调控微小RNA组成的复杂交互网络,以及这些相互作用影响癌症发展的方式,包括肿瘤血管生成、生长、侵袭和转移。基于微小RNA在癌症进展过程中对MMPs调控的决定性作用,我们从临床角度讨论了微小RNA介导的MMP调控在肿瘤诊断和治疗中的潜在应用。特别是,微小RNA介导的MMP调控可能会导致开发出更具选择性靶向MMPs的新型有前景的MMP抑制剂,并且这种方法还可能靶向网络中的多个分子,从而有效调控与恶性肿瘤相关的不同生物学过程。深入了解肿瘤进展过程中微小RNA介导的MMP调控机制,将有助于为恶性肿瘤的诊断和治疗提供新的见解。

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