microRNA研究进展

小分子RNA家族中的一员——microRNA,是一段非常短的非编码RNA序列,对多种生物学过程起调控作用。本文试从microRNA的结构特点、合成及作用机制和功能等方面对microRNA的研究进展作一个简单回顾。     

microRNA与心脏疾病

microRNA是植物和动物基因组编码的小分子非编码RNA.这种高度保守、长21～25个碱基RNA分子通过与mRNA的3'非编码区结合来调控基因组表达.microRNA通过其转录后调控机制在胚胎发育、细胞增殖,细胞分化、细胞死亡及细胞凋亡中发挥调控作用.近期研究发现,microRNA的异常表达可导致心脏疾病的发生、发展.现对microRNA在心脏发育、心肌肥厚和心肌重构、心力衰竭和心律失常等过程中的作用进行综述.     

microRNA识别和鉴定方法

microRNA是一类长约22nt的内源非编码小分子RNA,在线虫、果蝇、家鼠、人体及拟南芥等生物中普遍存在,并对其生长发育起着重要的调控作用。目前通过实验和计算机的方法在植物和动物中发现了越来越多的microRNA。通过对识别和鉴定新microRNA的主要方法策略的总结可以为microRNA今后的研究和发展提供一些思路和启发。     

MicroRNA在植物营养胁迫中的作用

microRNA是具有重要功能的一类非编码小RNA,不仅在植物生长发育过程中具有重要的调控作用,而且在植物营养胁迫中发挥作用。本文综述了microRNA在3种大量元素——氮、磷、硫胁迫中的作用。     

MicroRNA在胃癌中的作用及研究进展

MicroRNA(miRNA)是一类含有18-25个核苷酸的小分子非编码RNA,通过与与其靶基因mRNA 3’-非编码区的碱基互补配对,降解靶基因mRNA导致转录后沉默或者抑制靶基因mRNA的翻译过程,影响细胞的增殖、分化、衰老和凋亡.研究显示部分microRNA在胃癌组织中确实存在表达异常,且异常表达的microRNA通过对其靶基因表达的调控影响胃癌的发生、发展及转移等过程.外周血中microRNA检测技术的发展使得microRNA应用于胃癌的临床诊疗具有了一定的可行性.众多研究提示microRNA在胃癌的演进中的作用可能作为胃癌早期诊断和疗效预测的生物标记物,本文就microRNA在胃癌中的作用及研究进展作一综述.     

MicroRNA在神经系统不同部位特异分布及其在神经损伤再生中的变化和作用

MicroRNA是一类内源性的非编码RNA,在mRNA转录后水平调节靶基因的表达.近年来国内外研究表明,生理条件下microRNA在神经系统存在特异性表达并发挥重要作用.而在神经系统损伤后,多种microRNA的分布和表达发生改变,从而对神经再生过程产生影响.microRNA的这一作用对临床诊断和治疗神经系统损伤意义重大.     

microRNA在胚胎干细胞中的表达及作用

摘要: 胚胎干细胞是一类具有自我更新能力和多向分化潜能的细胞, 其自我更新和多向分化过程都在遗传和表观遗传的严格调控下进行的。越来越多的研究表明microRNA 也在这一过程中发挥重要的作用。microRNA是一类内源性的非编码RNA, 能够通过与靶mRNA特异性的结合而导致靶mRNA降解或抑制其翻译, 从而对基因进行转录后调控。文章就microRNA在胚胎干细胞中的表达及其作用的研究进展做一综述。主要讨论一些在胚胎干细胞中特异性表达的microRNA, 以及这些microRNA 对胚胎干细胞自我更新和未分化状态的维持和继续分化增殖的调控作用。     

MicroRNA在埃博拉病毒感染中的作用研究进展

MicroRNA是一类通过影响RNA表达、抑制蛋白质翻译来调节基因表达的内源性非编码小分子RNA。自从2014年首次发现苏丹型和扎伊尔型埃博拉病毒能够编码microRNA以来,不断有研究发现新的病毒microRNA以及其在埃博拉病毒复制、扩散、免疫逃逸中发挥的作用。宿主microRNA则参与到抗病毒防御机制中,但也面临着病毒蛋白对其调控的阻力包括相应宿主microRNA水平的变化以及RNA沉默抑制子的编码。深入研究埃博拉病毒与宿主在microRNA水平上的动态相互作用,有利于进一步了解埃博拉病毒的致病机制以及开发新的诊断、治疗策略。本文就microRNA在埃博拉病毒感染中的作用做一简要综述。     

水产虾蟹microRNA组学研究进展

MicroRNA是一类广泛存在于真核生物,长度约为18～25个核苷酸的非编码RNA,对靶基因转录后的调控具有重要作用,广泛参与生长发育、免疫、增殖和凋亡等各种生物学过程。本文简要总结了microRNA的生成、调控机制及其检测方法,讨论了虾蟹microRNA对免疫调控、生殖发育、环境胁迫三方面的调节作用,以期促进对虾蟹microRNA研究现状的了解以及为microRNA在虾蟹免疫、生殖发育和应对环境胁迫的调控机制研究提供参考。     

miR-132通过抑制转录共激活因子p300的活性调节抗病毒天然免疫应答

microRNA是小的非编码RNA,负向调节基因的表达。有研究表明microRNA具有先天的免疫调节作用,但其在病毒感染中的作用目前仍不清楚。该文通过研究人类致病性病毒——卡波济肉瘤相关疱疹病毒（KSHV）Nt其公认的天然细胞宿主——原代淋巴内皮细胞（LEC）,验证microRNA在病毒感染中的作用。     

miR-132 enhances dendritic morphogenesis, spine density, synaptic integration, and survival of newborn olfactory bulb neurons

An array of signals regulating the early stages of postnatal subventricular zone (SVZ) neurogenesis has been identified, but much less is known regarding the molecules controlling late stages. Here, we investigated the function of the activity-dependent and morphogenic microRNA miR-132 on the synaptic integration and survival of olfactory bulb (OB) neurons born in the neonatal SVZ. In situ hybridization revealed that miR-132 expression occurs at the onset of synaptic integration in the OB. Using in vivo electroporation we found that sequestration of miR-132 using a sponge-based strategy led to a reduced dendritic complexity and spine density while overexpression had the opposite effects. These effects were mirrored with respective changes in the frequency of GABAergic and glutamatergic synaptic inputs reflecting altered synaptic integration. In addition, timely directed overexpression of miR-132 at the onset of synaptic integration using an inducible approach led to a significant increase in the survival of newborn neurons. These data suggest that miR-132 forms the basis of a structural plasticity program seen in SVZ-OB postnatal neurogenesis. miR-132 overexpression in transplanted neurons may thus hold promise for enhancing neuronal survival and improving the outcome of transplant therapies.     

Upregulated miR-146a expression in peripheral blood mononuclear cells from rheumatoid arthritis patients

Introduction

MicroRNAs are small noncoding RNA molecules that negatively regulate gene expression via degradation or translational repression of their targeted mRNAs. It is known that aberrant microRNA expression can play important roles in cancer, but the role of microRNAs in autoimmune diseases is only beginning to emerge. In this study, the expression of selected microRNAs is examined in rheumatoid arthritis.

Methods

Total RNA was isolated from peripheral blood mononuclear cells obtained from patients with rheumatoid arthritis, and healthy and disease control individuals, and the expression of miR-146a, miR-155, miR-132, miR-16, and microRNA let-7a was analyzed using quantitative real-time PCR.

Results

Rheumatoid arthritis peripheral blood mononuclear cells exhibited between 1.8-fold and 2.6-fold increases in miR-146a, miR-155, miR-132, and miR-16 expression, whereas let-7a expression was not significantly different compared with healthy control individuals. In addition, two targets of miR-146a, namely tumor necrosis factor receptor-associated factor 6 (TRAF6) and IL-1 receptor-associated kinase 1 (IRAK-1), were similarly expressed between rheumatoid arthritis patients and control individuals, despite increased expression of miR-146a in patients with rheumatoid arthritis. Repression of TRAF6 and/or IRAK-1 in THP-1 cells resulted in up to an 86% reduction in tumor necrosis factor-α production, implicating that normal miR-146a function is critical for the regulation of tumor necrosis factor-α production.

Conclusions

Recent studies have shown that synovial tissue and synovial fibroblasts from patients with rheumatoid arthritis exhibit increased expression of certain microRNAs. Our data thus demonstrate that microRNA expression in rheumatoid arthritis peripheral blood mononuclear cells mimics that of synovial tissue/fibroblasts. The increased microRNA expression in rheumatoid arthritis patients is potentially useful as a marker for disease diagnosis, progression, or treatment efficacy, but this will require confirmation using a large and well defined cohort. Our data also suggest a possible mechanism contributing to rheumatoid arthritis pathogenesis, whereby miR-146a expression is increased but unable to properly function, leading to prolonged tumor necrosis factor-α production in patients with rheumatoid arthritis.     

MicroRNA and target protein patterns reveal physiopathological features of glioma subtypes

Gliomas such as oligodendrogliomas (ODG) and glioblastomas (GBM) are brain tumours with different clinical outcomes. Histology-based classification of these tumour types is often difficult. Therefore the first aim of this study was to gain microRNA data that can be used as reliable signatures of oligodendrogliomas and glioblastomas. We investigated the levels of 282 microRNAs using membrane-array hybridisation and real-time PCR in ODG, GBM and control brain tissues. In comparison to these control tissues, 26 deregulated microRNAs were identified in tumours and the tissue levels of seven microRNAs (miR-21, miR-128, miR-132, miR-134, miR-155, miR-210 and miR-409-5p) appropriately discriminated oligodendrogliomas from glioblastomas. Genomic, epigenomic and host gene expression studies were conducted to investigate the mechanisms involved in these deregulations. Another aim of this study was to better understand glioma physiopathology looking for targets of deregulated microRNAs. We discovered that some targets of these microRNAs such as STAT3, PTBP1 or SIRT1 are differentially expressed in gliomas consistent with deregulation of microRNA expression. Moreover, MDH1, the target of several deregulated microRNAs, is repressed in glioblastomas, making an intramitochondrial-NAD reduction mediated by the mitochondrial aspartate-malate shuttle unlikely. Understanding the connections between microRNAs and bioenergetic pathways in gliomas may lead to identification of novel therapeutic targets.     

Up-regulated microRNA-132 reduces the cognition-damaging effect of sevoflurane on Alzheimer's disease rats by inhibiting FOXA1

ObjectiveSome studies have implied the damaging effect of sevoflurane (sevo) on cognitive function in Alzheimer's disease (AD). This research was conducted to explore the effect of microRNA (miR)-132/forkhead-box A1 (FOXA1) axis on cognitive ability of sevo-treated AD rats.MethodsThe condensed-matter Aβ_1–40-induced AD rats were injected with miR-132- or FOXA1-related plasmids, followed by inhalation with 3% sevo. Then, the cognitive functions of AD rats were assessed. miR-132 and FOXA1 levels in hippocampal tissues of AD rats, and their interaction were identified.ResultsmiR-132 expression was reduced and FOXA1 mRNA and protein levels were elevated in AD rats. miR-132 targeted FOXA1. Sevo treatment impaired cognitive function in AD rats. Elevated miR-132 or inhibited FOXA1 attenuated sevo-mediated injury in AD rats. Overexpressed FOXA1 rescued the effect of elevated miR-132 in AD rats with sevo treatment.ConclusionUp-regulated miR-132 reduces the cognition-damaging effect of sevo on AD rats by inhibiting FOXA1.     

MicroRNA Regulation of the Synaptic Plasticity-Related Gene Arc

Expression of activity-regulated cytoskeleton associated protein (Arc) is crucial for diverse types of experience-dependent synaptic plasticity and long-term memory in mammals. However, the mechanisms governing Arc-specific translation are little understood. Here, we asked whether Arc translation is regulated by microRNAs. Bioinformatic analysis predicted numerous candidate miRNA binding sites within the Arc 3'-untranslated region (UTR). Transfection of the corresponding microRNAs in human embryonic kidney cells inhibited expression of an Arc 3'UTR luciferase reporter from between 10 to 70% across 16 microRNAs tested. Point mutation and deletion of the microRNA-binding seed-region for miR-34a, miR-326, and miR-19a partially or fully rescued reporter expression. In addition, expression of specific microRNA pairs synergistically modulated Arc reporter expression. In primary rat hippocampal neuronal cultures, ectopic expression of miR-34a, miR-193a, or miR-326, downregulated endogenous Arc protein expression in response to BDNF treatment. Conversely, treatment of neurons with cell-penetrating, peptide nucleic acid (PNA) inhibitors of miR-326 enhanced Arc mRNA expression. BDNF dramatically upregulated neuronal expression of Arc mRNA and miR-132, a known BDNF-induced miRNA, without affecting expression of Arc-targeting miRNAs. Developmentally, miR-132 was upregulated at day 10 in vitro whereas Arc-targeting miRNAs were downregulated. In the adult brain, LTP induction in the dentate gyrus triggered massive upregulation of Arc and upregulation of miR-132 without affecting levels of mature Arc-targeting miRNAs. Turning to examine miRNA localization, qPCR analysis of dentate gyrus synaptoneurosome and total lysates fractions demonstrated synaptic enrichment relative to small nucleolar RNA. In conclusion, we find that Arc is regulated by multiple miRNAs and modulated by specific miRNA pairs in vitro. Furthermore, we show that, in contrast to miR-132, steady state levels of Arc-targeting miRNAs do not change in response to activity-dependent expression of Arc in hippocampal neurons in vitro or during LTP in vivo.     

Circulating microRNA 132-3p and 324-3p Profiles in Patients after Acute Aneurysmal Subarachnoid Hemorrhage

Background

Aneurysmal subarachnoid hemorrhage (SAH) is a highly morbid and fatal condition with high rate of cognitive impairment and negative impact in quality of life among survivors. Delayed cerebral infarction (DCI) is one the major factors for these negative outcomes. In this study we compared the circulating microRNA profiles of SAH patients and healthy individuals, and the circulating microRNA profiles of SAH patients with and without DCI.

Methods

Peripheral blood samples on Day 7 after the onset of SAH were subjected to microarray analysis with Affymetrix miRNA 3.0 array and quantitative PCR analysis. SAH patients with (N = 20) and without DCI (N = 20) and Healthy controls (N = 20) were included for analyses.

Results

We demonstrated that 99 miRNAs were found to be dysregulated in the SAH patient group with DCI. 81 miRNAs were upregulated and 18 were downregulated. Findings from KEGG pathway analysis showed that miRNAs and target genes for axon guidance and TGF-beta signaling were involved, implying that the resulted differential miRNA expression pattern reflect the results of SAH instead of etiology of the disease. miR-132-3p and miR-324-3p showed distinctive upregulations in qPCR [miR-132: 9.5 fold (95%CI: 2.3 to 16.7) in DCI group and 3.4 fold (95%CI: 1.0 to 5.8) in Non-DCI group; miR-324: 4924 fold (95%CI: 2620 to 7228) in DCI group and 4545 fold (95%CI: 2408 to 6683) in non-DCI group]. However, there were no significant differences in fold changes between SAH patients with and without DCI [fold change ratios (mean+/-SD): 2.7+/-4.2 and 1.1+/-1.1 for miRNA-132 and miRNA-324].

Conclusion

Our study demonstrated that as compared to healthy control, miR-132 and miR-324 showed a upregulation in both SAH DCI and Non-DCI groups. However, the differences between the SAH DCI and non-DCI groups were not statistically significant.     

与胃癌发生相关MicroRNA 的研究新进展

MicroRNA(微小核糖核酸;miRNA)是一类长约20～25个核苷酸的非编码的单链RNA分子.它的表达与个体发育、增殖、分化以及恶性肿瘤发生密切相关[1,2].近期研究表明microRNA具有癌基因和抑癌基因的作用.新研究发现miR-20b,miR-150,miR- 106a,miR-27a,miR107,miR-21,miR-20a与胃癌的发生过程呈正相关;而Let-7microRNA,miR-218,miR-101,miR-650,miR-29,miR-34,miR-451与胃癌的发生过程呈负相关.本文就胃癌发生相关microRNA的研究新进展予以综述.