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微小 RNA 作为皮肤发育、稳态和疾病中的新型调控因子。

MicroRNAs as novel players in skin development, homeostasis and disease.

机构信息

Gene Center, LMU Munich, Feodor-Lynen-Strasse 25, 81377 Munich, Germany.

出版信息

Br J Dermatol. 2012 Jan;166(1):22-8. doi: 10.1111/j.1365-2133.2011.10568.x. Epub 2011 Nov 4.

Abstract

MicroRNAs (miRNAs) are a group of newly discovered small (∼19-24 nucleotides), noncoding RNAs that modulate gene expression by interacting with the 3' untranslated region of the corresponding target gene messenger RNA (mRNA). miRNAs have been estimated to regulate more than one-third of protein-encoding mRNAs. As a consequence, cellular protein expression and a large number of biological processes are influenced by miRNA-mediated post-transcriptional regulation of gene expression. The severe phenotype of mice lacking key enzymes of the miRNA biogenesis pathway (Dgcr8 and Dicer) in the skin confirmed the essential function of miRNAs in this tissue. In addition, a growing number of reports has identified miRNAs as regulators of the morphogenesis and homeostasis of the skin and its appendages, and miRNA deregulation was shown to be associated or even causally related to several skin diseases. Profiling studies have identified numerous differentially regulated miRNAs associated with physiological (e.g. keratinocyte differentiation) and pathological (e.g. psoriasis, melanoma) processes. These data bear enormous potential for further studies. Because of the easy accessibility of the skin, it is plausible to anticipate that, once efficient and safe methods for the topical delivery of substances mimicking or modulating miRNA activity become available, skin diseases will be among the first to be approached with miRNA-based therapies. This review article gives a short introduction to miRNA biology and summarizes and discusses existing evidence for a role of these molecules in the skin.

摘要

微小 RNA(miRNA)是一组新发现的小型(约 19-24 个核苷酸)非编码 RNA,通过与相应靶基因信使 RNA(mRNA)的 3'非翻译区相互作用来调节基因表达。据估计,miRNA 可以调节超过三分之一的蛋白质编码 mRNA。因此,细胞蛋白表达和大量生物学过程受到 miRNA 介导的基因表达转录后调控的影响。在皮肤中缺乏 miRNA 生物发生途径关键酶(Dgcr8 和 Dicer)的小鼠的严重表型证实了 miRNA 在该组织中的重要功能。此外,越来越多的报道已经确定了 miRNA 作为皮肤及其附属物形态发生和动态平衡的调节剂,并且 miRNA 失调与几种皮肤疾病相关甚至因果相关。分析研究已经确定了许多与生理(例如角质形成细胞分化)和病理(例如银屑病、黑色素瘤)过程相关的差异调节 miRNA。这些数据具有进一步研究的巨大潜力。由于皮肤易于接近,因此可以预料,一旦获得模拟或调节 miRNA 活性的物质的有效和安全的局部递送方法,皮肤疾病将成为 miRNA 治疗的首批治疗对象之一。本文综述了 miRNA 生物学,并总结和讨论了这些分子在皮肤中的作用的现有证据。

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