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MicroRNAs 生物学研究进展。

Insights in microRNAs biology.

机构信息

Cellular and Molecular Biomechanics Unit, Department of Biological Chemistry, Medical School, University of Athens, 75, M. Asias Street, 11527 Athens, Greece.

出版信息

Curr Top Med Chem. 2013;13(13):1493-502. doi: 10.2174/15680266113139990098.

Abstract

MicroRNAs (miRNAs) are small, non-coding RNAs, that function as post-transcriptional regulators of gene expression. Recent studies now predict that numerous miRNA molecules regulate a large proportion of the human transcriptome, thus creating a whole new research field that utilizes their potential impact on gene expression in favor of diagnosis, prognosis and drug development. MiRNAs are generated from transcription of respective genes into primary structures that usually follow a two-step maturation process in the cell nucleus and cytoplasm. Active miRNA folds downregulate protein expression either via direct repression of targeted messenger RNA (mRNA) or mRNA cleavage. They are critical factors that control human development and organogenesis and reemerge as key-molecules that profoundly influence adult cells and tissues under stress-responsive conditions. Therefore, several miRNAs exhibit dysregulated functions in almost all aspects of human pathology such as cancer, cardiovascular diseases, metabolic disorders, genetic and neurodegenerative diseases, forming tissue-specific molecular profiles that further define salient pathologic features. The present article offers an overview on miRNAs biogenesis and functional processes, major aspects of their participation in human development and milestones regarding their contribution in human diseases. Furthermore, their utility as extracellular biomarkers and the rationale behind miRNA inhibition or miRNA delivery are being discussed.

摘要

微小 RNA(miRNA)是一类小的非编码 RNA,作为基因表达的转录后调控因子发挥作用。最近的研究表明,许多 miRNA 分子调节了人类转录组的很大一部分,从而创造了一个全新的研究领域,利用它们对基因表达的潜在影响来支持诊断、预后和药物开发。miRNA 是由各自基因的转录产生的,通常遵循细胞核和细胞质中的两步成熟过程。活性 miRNA 折叠通过直接抑制靶向信使 RNA(mRNA)或 mRNA 切割来下调蛋白质表达。它们是控制人类发育和器官发生的关键因素,并重新成为在应激反应条件下深刻影响成年细胞和组织的关键分子。因此,几乎在人类病理学的所有方面,如癌症、心血管疾病、代谢紊乱、遗传和神经退行性疾病,都存在 miRNA 功能失调,形成组织特异性分子谱,进一步定义明显的病理特征。本文概述了 miRNA 的生物发生和功能过程、它们在人类发育中的主要参与方面以及它们在人类疾病中的贡献的里程碑。此外,还讨论了它们作为细胞外生物标志物的用途以及 miRNA 抑制或 miRNA 递送来抑制 miRNA 功能的基本原理。

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