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微小 RNA 作为癌症治疗的新靶点和工具。

MicroRNAs as novel targets and tools in cancer therapy.

机构信息

Department of Experimental Surgery, Medical Faculty Mannheim, and Center for Biomedicine and Medical Technology Mannheim (CBTM), Ruprecht-Karls University of Heidelberg, Ludolf-Krehl-Str. 6, 68135 Mannheim, Germany.

Department of Regenerative Medicine and Immune Regulation, Medical University of Bialystok, ul. Waszyngtona 13, 15-269 Bialystok, Poland.

出版信息

Cancer Lett. 2017 Feb 28;387:84-94. doi: 10.1016/j.canlet.2016.03.043. Epub 2016 Apr 1.

Abstract

MicroRNAs (miRNAs) are currently experiencing a renewed peak of attention not only as diagnostics but also especially as highly promising novel targets or tools for clinical therapy in several different malignant diseases. Moreover, the recent discovery of competing endogenous RNAs (ceRNAs) as novel miRNA-regulators has contributed exciting insights in this regard. Therefore, this review summarizes and discusses the latest findings on (1) how miRNAs have become therapeutic targets of diverse synthetic antagonists, (2) how novel endogenous regulators of miRNAs such as ceRNAs or pseudogenes could emerge as therapeutics scavenging oncogenic miRNAs and (3) how miRNAs themselves are already, and will increasingly be, used as therapeutics. Recent advances on the importance of miRNA-target affinity and the subcellular localization of miRNAs are also discussed. The potential of these developments in different tumor entities and particular hallmarks of cancer such as metastasis, disease progression, interactions with the tumor microenvironment, or cancer stem cells are equally highlighted.

摘要

MicroRNAs (miRNAs) 目前不仅作为诊断标志物再次受到高度关注,而且作为几种不同恶性疾病临床治疗的极具前景的新型靶点或工具也备受关注。此外,最近发现竞争性内源性 RNA (ceRNA) 作为新型 miRNA 调节剂,为此提供了令人兴奋的见解。因此,本综述总结和讨论了关于(1)miRNAs 如何成为各种合成拮抗剂的治疗靶点,(2)miRNAs 的新型内源性调节剂,如 ceRNA 或假基因,如何作为清除致癌 miRNA 的治疗剂出现,以及(3)miRNAs 本身如何以及将越来越多地用作治疗剂的最新发现。还讨论了 miRNA 靶标亲和力和 miRNA 亚细胞定位的重要性的最新进展。同样强调了这些发展在不同肿瘤实体和癌症的特定标志中的潜力,如转移、疾病进展、与肿瘤微环境或癌症干细胞的相互作用。

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