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微小RNA在翻译调控及癌症中的作用

Role of microRNAs in translation regulation and cancer.

作者信息

Oliveto Stefania, Mancino Marilena, Manfrini Nicola, Biffo Stefano

机构信息

Stefania Oliveto, Marilena Mancino, Nicola Manfrini, Stefano Biffo, INGM, National Institute of Molecular Genetics "Romeo ed Enrica Invernizzi", 20122 Milano, Italy.

出版信息

World J Biol Chem. 2017 Feb 26;8(1):45-56. doi: 10.4331/wjbc.v8.i1.45.

Abstract

MicroRNAs (miRNAs) are pervasively expressed and regulate most biological functions. They function by modulating transcriptional and translational programs and therefore they orchestrate both physiological and pathological processes, such as development, cell differentiation, proliferation, apoptosis and tumor growth. miRNAs work as small guide molecules in RNA silencing, by negatively regulating the expression of several genes both at mRNA and protein level, by degrading their mRNA target and/or by silencing translation. One of the most recent advances in the field is the comprehension of their role in oncogenesis. The number of miRNA genes is increasing and an alteration in the level of miRNAs is involved in the initiation, progression and metastases formation of several tumors. Some tumor types show a distinct miRNA signature that distinguishes them from normal tissues and from other cancer types. Genetic and biochemical evidence supports the essential role of miRNAs in tumor development. Although the abnormal expression of miRNAs in cancer cells is a widely accepted phenomenon, the cause of this dysregulation is still unknown. Here, we discuss the biogenesis of miRNAs, focusing on the mechanisms by which they regulate protein synthesis. In addition we debate on their role in cancer, highlighting their potential to become therapeutic targets.

摘要

微小RNA(miRNA)广泛表达并调控大多数生物学功能。它们通过调节转录和翻译程序发挥作用,因此协调生理和病理过程,如发育、细胞分化、增殖、凋亡和肿瘤生长。miRNA在RNA沉默中作为小向导分子发挥作用,通过在mRNA和蛋白质水平上负调控多个基因的表达,降解其mRNA靶标和/或使翻译沉默。该领域最新进展之一是对其在肿瘤发生中作用的理解。miRNA基因数量不断增加,miRNA水平的改变与多种肿瘤的起始、进展和转移形成有关。一些肿瘤类型表现出独特的miRNA特征,使其与正常组织及其他癌症类型区分开来。遗传学和生物化学证据支持miRNA在肿瘤发展中的重要作用。尽管癌细胞中miRNA的异常表达是一个广泛接受的现象,但其失调的原因仍不清楚。在此,我们讨论miRNA的生物合成,重点关注它们调节蛋白质合成的机制。此外,我们还探讨它们在癌症中的作用,强调其成为治疗靶点的潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/509b/5329714/ab6ea36dbb94/WJBC-8-45-g001.jpg

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