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微小RNA-21作为癌症和心血管疾病的治疗靶点。

MicroRNA-21 as therapeutic target in cancer and cardiovascular disease.

作者信息

Bonci Désirée

机构信息

Department of Hematology, Oncology and Molecular Medicine, Istituto Superiore Sanità, Rome, Italy.

出版信息

Recent Pat Cardiovasc Drug Discov. 2010 Nov;5(3):156-61. doi: 10.2174/157489010793351962.

Abstract

MicroRNAs (miRNAs) are a broad class of small non-coding RNAs that control expression of complementary target messenger RNAs. Dysregulation of miRNAs has been described in various disease states including cancer and cardiac disease. A particular miRNA that was consistently reported to be upregulated in both cancer and various forms of cardiovascular diseases is miR-21. MiR-21 exerts oncogenic activity and therefore is considered as an oncomir. In the cardiovascular system miR-21 is enriched in fibroblasts and contributes to the development of fibrosis and heart failure. MiR-21 therefore emerges as an interesting candidate for the development of therapeutic strategies against many forms of cancer as well as heart diseases. Indeed, treatment with anti-miR-21 oligonucleotides reduced breast cancer growth. Inhibition of miR-21 by synthetic miRNA antagonists (antagomirs) improved heart function in a cardiac disease model. The same beneficial effects were observed in miR-21 knockout mice subjected to pressure-overload of the left ventricle underlining the key role of miR-21 as a therapeutic target. We here overview the current patent situation about the therapeutic use of miR-21 modulation in cancer and cardiovascular disease.

摘要

微小RNA(miRNA)是一类广泛存在的小非编码RNA,可控制互补靶信使RNA的表达。在包括癌症和心脏病在内的各种疾病状态中,均已发现miRNA表达失调。一种在癌症和各种心血管疾病中均持续被报道上调的特定miRNA是miR-21。miR-21具有致癌活性,因此被视为一种癌基因miRNA。在心血管系统中,miR-21在成纤维细胞中富集,并促进纤维化和心力衰竭的发展。因此,miR-21成为开发针对多种癌症和心脏病治疗策略的一个有吸引力的候选靶点。事实上,用抗miR-21寡核苷酸治疗可减少乳腺癌的生长。在一种心脏病模型中,合成的miRNA拮抗剂(抗miR)抑制miR-21可改善心脏功能。在左心室压力过载的miR-21基因敲除小鼠中也观察到了同样的有益效果,这突出了miR-21作为治疗靶点的关键作用。我们在此概述了目前关于miR-21调控在癌症和心血管疾病治疗应用方面的专利情况。

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