Semmelweis University, Institute of Pathophysiology, Budapest, Hungary.
Adv Drug Deliv Rev. 2010 Nov 30;62(14):1390-401. doi: 10.1016/j.addr.2010.10.003. Epub 2010 Oct 19.
Micro RNAs (miRNAs) are a recently discovered class of small, non-coding RNAs with the function of post-transcriptional gene expression regulation. MiRNAs may function in networks, forming a complex relationship with diseases. Alterations of specific miRNA levels have significant correlation with diseases of divergent origin, such as diabetic or ischemic organ injury including nephropathy, and malignant diseases including renal tumors. After identification of disease-associated miRNAs, there are two options of influencing their tissue expression. The function of miRNAs can be inhibited by antisense oligonucleotides (ASOs), which have been shown to silence specific miRNAs in vivo. Moreover, miRNA activity can be also mimicked or enhanced by delivering chemically synthesized miRNAs. Thus, modifying the expression of miRNAs is a potential future gene-therapeutic tool to influence posttranscriptional regulation of multiple genes in a single therapy. In this review we focus on key renal miRNAs with the aim of revealing the pathomechanisms of renal diseases. Nucleic acid therapy with oligonucleotides and short interfering RNA (siRNA) are under clinical evaluation presently. Similar therapeutic strategies, to influence miRNA function is also already under clinical investigation in RNA interference trials. We summarize here studies specifically aimed at the modification of miRNA expression. Research on the post-transcriptional regulation of gene expression by miRNA may reshape our understanding of renal pathophysiology and consequently may bring new diagnostic markers and therapeutic agents.
微小 RNA(miRNAs)是一类新发现的小非编码 RNA,具有转录后基因表达调控的功能。miRNAs 可能在网络中发挥作用,与疾病形成复杂的关系。特定 miRNA 水平的改变与不同起源的疾病有显著相关性,如糖尿病或缺血性器官损伤包括肾病,以及恶性疾病包括肾肿瘤。在鉴定出与疾病相关的 miRNAs 后,有两种影响其组织表达的选择。可以通过反义寡核苷酸(ASO)抑制 miRNA 的功能,ASO 已被证明可以在体内沉默特定的 miRNA。此外,还可以通过递送化学合成的 miRNAs 来模拟或增强 miRNA 的活性。因此,修饰 miRNA 的表达是一种潜在的未来基因治疗工具,可以在单次治疗中影响多个基因的转录后调控。在这篇综述中,我们重点介绍了关键的肾脏 miRNAs,旨在揭示肾脏疾病的发病机制。目前正在对寡核苷酸和小干扰 RNA(siRNA)的核酸治疗进行临床评估。类似的治疗策略,即影响 miRNA 功能,也已经在 RNA 干扰试验的临床试验中进行了研究。我们在这里总结了专门针对 miRNA 表达修饰的研究。miRNA 对基因表达的转录后调控的研究可能会改变我们对肾脏病理生理学的理解,从而可能带来新的诊断标志物和治疗药物。