The role of microRNAs in HIV-1 pathogenesis and therapy

There has been a paradigm shift in our understanding of how protein regulation occurs within mammalian cells in the last 15 years. Our current understanding is that small, noncoding RNA molecules called microRNAs (miRNAs) play a vital role in modulating the translation of mRNAs into protein. Important studies suggest that HIV-1 replication may be restricted by certain host cellular miRNAs, and this in turn may play pivotal roles in host defense and in maintaining latency within resting CD4 T cells. Conversely, host cellular miRNAs have also been demonstrated to be essential for certain viruses to establish infection and the altered expression of cellular miRNAs in the setting of HIV-1 may also be a factor favoring viral replication. The differential expression of important protective histocompatability locus antigen (HLA) alleles in HIV-1 infection has recently been shown to be regulated by miRNAs. To date, most efforts into finding an effective vaccine to combat HIV-1 have not been successful. Understanding the role that miRNAs may play in HIV-1 pathogenesis may allow a different approach to targeting key small RNAs or the identification of new important protein targets regulated by miRNAs, which may result in a better vaccine construct. The purpose of this review is to look at our current state of understanding of how HIV-1 and the miRNA pathway interact and the possible therapeutic interventions that this knowledge may entail.     

MicroRNAs in Allergy and Asthma

microRNAs (miRNAs) are short, single-stranded RNA molecules that function together with the partner proteins and cause degradation of target mRNAs or inhibit their translation. A particular miRNA can have hundreds of targets; therefore, miRNAs cumulatively influence the expression of a large proportion of genes. The functions of miRNAs in human diseases have been studied since their discovery in mammalian cells approximately 12 years ago. However, the role of miRNAs in allergic disease has only very recently begun to be uncovered. The purpose of this review is to provide an overview of the functions of miRNAs involved in the development of allergic diseases. We describe here the functions of miRNAs that regulate Th2 polarization and influence general inflammatory and tissue responses. In addition, we will highlight findings about the functions of extracellular miRNAs as possible noninvasive biomarkers of diseases with heterogeneous phenotypes and complex mechanisms and briefly discuss advances in the development of miRNA-based therapeutics.     

Dicer loss in striatal neurons produces behavioral and neuroanatomical phenotypes in the absence of neurodegeneration

MicroRNAs (miRNAs) are small noncoding RNAs that can act to repress target mRNAs by suppressing translation and/or reducing mRNA stability. Although it is clear that miRNAs and Dicer, an RNase III enzyme that is central to the production of mature miRNAs, have a role in the early development of neurons, their roles in the postmitotic neuron in vivo are largely unknown. To determine the roles of Dicer in neurons, we ablated Dicer in dopaminoceptive neurons. Mice that have lost Dicer in these cells display a range of phenotypes including ataxia, front and hind limb clasping, reduced brain size, and smaller neurons. Surprisingly, dopaminoceptive neurons without Dicer survive over the life of the animal. The lack of profound cell death contrasts with other mouse models in which Dicer has been ablated. These studies highlight the complicated nature of Dicer ablation in the brain and provide a useful mouse model for studying dopaminoceptive neuron function.     

microRNA在过敏性哮喘中的作用

microRNA(miRNA)是一种短单链小分子RNA,与蛋白质一起形成RNA诱导沉默复合体,引起靶mRNA的降解或抑制其翻译,所以miRNA的变化可影响机体大部分基因的表达。自从在哺乳动物细胞中被发现后,miRNA在过敏性疾病中的重要作用近些年来正逐步得到研究者重视。该文综述了miRNA在过敏性哮喘中的功能,主要包括miRNA的生成、调节辅助T细胞极化、在炎性反应和组织反应中的变化,胞外miRNA作为过敏性哮喘诊断的生物指标;并对miRNAs在未来的研究和应用进行展望。     

MicroRNA-based therapeutic approaches in the cardiovascular system

MicroRNAs (miRNAs) are endogenous small ribonucleotides that participate in the orchestration of the genome by regulating target messenger RNA translation. MiRNAs control physiological processes and misexpression of miRNAs is pathogenically involved in many diseases including cardiovascular diseases. Normalization of miRNA expression and thus downstream target networks may have enormous therapeutic chances but also risks. We here highlight and discuss recent advances in the development and use of miRNA therapeutics to target miRNAs in vivo that may translate into novel therapeutic strategies for cardiovascular diseases in the future.     

MicroRNAs作为大肠癌生物标志物的研究进展

MicroRNAs(miRNAs)是一种短链(19-24个核苷酸)非编码RNA,可抑制蛋白质翻译或其靶基因mRNAs的降解,因而在基因表达调控中发挥重要作用.最近的研究发现存在于大肠癌(colorectal cancer,CRC)组织和血液中的miRNAs可较准确地诊断大肠癌的存在,并帮助判断CRC临床病理特征及预测疾病复发,特异miRNAs的过表达和沉默与CRC的发生发展相关,且其在CRC组织和血液中的差异表达为早期筛选和诊断CRC提供了应用前景.另外,miRNAs可能成为CRC基因治疗的重要靶点.本文将就miRNAs作为生物标志物在CRC诊治中的潜在作用作一综述.     

Integrating the MicroRNome into the study of lung disease

Over the last 15 years, investigators have identified small noncoding RNAs as regulators of gene expression. One type of noncoding RNAs are termed microRNAs (miRNAs). miRNAs are evolutionary conserved, approximately 22-nucleotide single-stranded RNAs that target genes by inducing mRNA degradation or by inhibiting translation. miRNAs are implicated in many critical cellular processes, including apoptosis, proliferation, and differentiation. Furthermore, it is estimated that miRNAs may be responsible for regulating the expression of nearly one-third of the human genome. Despite the identification of greater than 500 mature miRNAs, very little is known about their biological functions and functional targets. In the last 5 years, researchers have increasingly focused on the functional relevance and role that miRNAs play in the pathogenesis of human disease. miRNAs are known to be important in solid organ and hematological malignancies, heart disease, as potential modulators of the immune response, and organ development. It is anticipated that miRNA analysis will emerge as an important complement to proteomic and genomic studies to further our understanding of disease pathogenesis. Despite the application of genomics and proteomics to the study of human lung disease, few studies have examined miRNA expression. This perspective is not meant to be an exhaustive review of miRNA biology but will provide an overview of both miRNA biogenesis and our current understanding of the role of miRNAs in lung disease as well as a perspective on the importance of integrating this analysis as a tool for identifying and understanding the biological pathways in lung-disease pathogenesis.     

Novel techniques and targets in cardiovascular microRNA research

MicroRNAs (miRNAs) are highly conserved, tiny (～22 nucleotides) non-coding RNAs that have emerged as potent regulators of mRNA translation. miRNAs exhibit fine-tuning of the control of proteins involved in cell signalling (AE) pathways and in vital cellular and developmental processes. miRNAs are expressed in cardiovascular tissues, and multiple functional aspects of miRNAs underscore their key role in cardiovascular (patho)physiology. The development and increasing use of novel molecular biology tools have contributed to the recent success in miRNA research. In the present review, we discuss current updates on important and novel miRNA techniques, including: (i) miRNA screening tools; (ii) bioanalytical target prediction tools; (iii) target validation tools; and (iv) manipulative miRNA expression tools. We also present an update about recently identified miRNA targets that play a key role in cardiovascular development and disorders.     

MicroRNAs与骨质疏松症研究

MicroRNAs（miRNAs or miRs）为一种新的基因调控机制,MicroRNAs是由22个核苷酸组成的内源性非编码小分子RNA,调节蛋白翻译和mRNA的稳定。间充质干细胞（mesenchymal stem cells,MSCs）分化异常与骨质疏松症的发生有着密切关系。最近研究发现miRNAs在MSCs分化过程中发挥着重要的调控作用,但具体调控机制尚未完全阐明。进一步深入研究miRNAs在MSCs中的作用,全面了解MSCs分化的机制,对骨质疏松症的预防和治疗有重要意义。     

Mammalian Pumilio 2 regulates dendrite morphogenesis and synaptic function

In Drosophila, Pumilio (Pum) is important for neuronal homeostasis as well as learning and memory. We have recently characterized a mammalian homolog of Pum, Pum2, which is found in discrete RNA-containing particles in the somatodendritic compartment of polarized neurons. In this study, we investigated the role of Pum2 in developing and mature neurons by RNA interference. In immature neurons, loss of Pum2 led to enhanced dendritic outgrowth and arborization. In mature neurons, Pum2 down-regulation resulted in a significant reduction in dendritic spines and an increase in elongated dendritic filopodia. Furthermore, we observed an increase in excitatory synapse markers along dendritic shafts. Electrophysiological analysis of synaptic function of neurons lacking Pum2 revealed an increased miniature excitatory postsynaptic current frequency. We then identified two specific mRNAs coding for a known translational regulator, eIF4E, and for a voltage-gated sodium channel, Scn1a, which interacts with Pum2 in immunoprecipitations from brain lysates. Finally, we show that Pum2 regulates translation of the eIF4E mRNA. Taken together, our data reveal a previously undescribed role for Pum2 in dendrite morphogenesis, synapse function, and translational control.     

Circulating microRNAs: novel biomarkers and extracellular communicators in cardiovascular disease?

In the past few years, the crucial role of different micro-RNAs (miRNAs) in the cardiovascular system has been widely recognized. Recently, it was discovered that extracellular miRNAs circulate in the bloodstream and that such circulating miRNAs are remarkably stable. This has raised the possibility that miRNAs may be probed in the circulation and can serve as novel diagnostic markers. Although the precise cellular release mechanisms of miRNAs remain largely unknown, the first studies revealed that these circulating miRNAs may be delivered to recipient cells, where they can regulate translation of target genes. In this review, we will discuss the nature of the stability of miRNAs that circulate in the bloodstream and discuss the available evidence regarding the possible function of these circulating miRNAs in distant cell-to-cell communication. Furthermore, we summarize and discuss the usefulness of circulating miRNAs as biomarkers for a wide range of cardiovascular diseases such as myocardial infarction, heart failure, atherosclerosis, hypertension, and type 2 diabetes mellitus.