miRNA对T细胞分化与功能的调节作用

miRNA是一类长度为19~24 nt的内源性非编码小分子RNA,主要通过抑制mRNA的翻译或使其降解对靶基因实现转录后水平的调控。miRNA与T细胞的分化及功能密切相关,参与自身免疫性疾病、感染性疾病、肿瘤等多种病理过程的免疫调控。本文综述了近年来发现的miRNA在T细胞分化与功能调节中的作用,特别是其在抗感染与抗肿瘤免疫中的作用。     

miRNA在白血病中的研究进展

microRNA(miRNA)是一种小分子非编码RNA,在细胞增殖、分化和凋亡等多种生理过程中发挥着重要作用.白血病相关miRNA研究进展迅速,并呈现了miRNA介导白血病瘤细胞增殖、分化和凋亡的调控网络.深入了解相关miRNA与白血病的发生、发展关系将为白血病的治疗开辟新途径.     

MicroRNA对胚胎干细胞的多能性网络调控

胚胎干细胞(Embryonic stem cells, ESCs)是一类能够无限增殖和诱导分化为多种类型细胞的干细胞。MicroRNA(miRNA)是一类内源性具有调控基因表达功能的非编码RNA, 在ESCs增殖和分化过程中起重要作用。MiRNA可以通过对ESCs多能性网络中的转录因子、细胞周期、表观遗传学、信号转导等方面调控, 促使ESCs维持多能性状态。文章重点综述了miRNA的生成过程、调控ESCs多能性的主要miRNA家族以及miRNA对ESCs多能性网络调控作用等内容。     

蜜蜂microRNA的研究进展

MicroRNA (miRNA)是一类长度为18~24 nt的内源性非编码小RNA分子,它能通过与靶标mRNA 分子互补结合抑制蛋白质翻译或导致 mRNA 降解,从而调控靶基因表达。蜜蜂是重要的社会性经济昆虫,一直是国际上热门的研究对象。迄今为止,通过各种生物技术在蜜蜂中发现已鉴定注册的miRNA共有218个,对蜜蜂miRNA的研究表明其在蜜蜂的胚胎发育、级型分化、劳动分工和免疫防御等方面可能具有重要的调控作用。本文就miRNA对蜜蜂蜂王和工蜂级型分化、哺育蜂和采集蜂劳动分工、舞蹈行为、脑部神经功能及免疫防御等方面调控作用的最新研究进展进行了综述,以期为进一步研究miRNA提供借鉴和参考。     

昆虫microRNA的研究进展

MicroRNA (miRNA)是20世纪90年代发现的一类由内源基因编码的长度约21~24 nt的非编码单链RNA分子, 广泛存在于真核生物中, 对基因的转录后调控起着非常重要的作用。本文简要介绍了miRNA的产生与调控机制, 同时从昆虫miRNA的发现鉴定、 靶基因预测与功能验证, 昆虫miRNA的序列特征与进化, 果蝇和非果蝇类昆虫miRNA生物学功能以及供昆虫miRNA研究的网络平台等方面对昆虫miRNA的最新进展进行了综述, 旨在为进一步研究昆虫miRNA提供借鉴和参考。对昆虫miRNA的研究表明其参与调控细胞分化、 增殖及凋亡、 胚胎发育、 器官发生、 形态构建、 生理代谢、 环境协调、 行为认知、 免疫防御等几乎所有的生物过程。因此, 深入研究其生物功能、 调控网络和开发应用等可能成为今后一段时间昆虫miRNA研究的重要内容。     

MicroRNA及其在昆虫学中的研究进展

MicroRNA(miRNA)是真核生物中对转录后调控起着重要作用的一类非编码单链RNA分子,参与调控胚胎发育、干细胞分化、神经发生及细胞凋亡等几乎所有的生物过程。本文简要总结了miRNA的生物合成、命名、表达及功能等方面的研究进展,同时从昆虫miRNA的鉴定、表达及功能、miRNA的代谢等方面对miRNA在昆虫学研究中的最新进展做了综述。     

MicroRNA 与肿瘤的相关研究进展

微小RNA(microRNAs,miRNA)是一类22个核苷酸左右的非编码调控RNA。可以通过切割mRNA或者是抑制翻译两种机制,在转录后水平发挥调控生物生长发育的重要作用。目前的研究已经发现microRNA参与调控发育、细胞分化、细胞凋亡等多种生理过程。目前已证实miRNA参与肿瘤发生和进展,miRNA表达谱是肿瘤诊断和预后的指标,miRNA突变、缺失或表达水平的异常与人类肿瘤密切相关,它发挥类似于癌基因或抑癌基因的作用,参与肿瘤细胞的增殖、分化和细胞凋亡过程。本文就miRNA在肿瘤发生发展以及诊断治疗方面的研究进展作一综述。     

实时荧光定量PCR相对定量法检测循环miRNA的内参选择

microRNA(miRNA)是一类内源性非编码微小RNA,在调控细胞增殖、分化、凋亡等方面发挥重要作用。研究发现,miRNA能够稳定存在于细胞外液,被称为循环miRNA。在多种疾病状态下循环miRNA表达谱改变,具有成为非创伤性新型生物标志物的潜能。实时荧光定量PCR(RT-qPCR)是检测miRNA表达变化的确证实验,其中内参的选择关系到相对定量结果是否真实可靠。我们简要综述国内外实验室常用的RT-qPCR内参及其特点。     

miRNA功能的研究进展

综述了miRNA功能的最新研究进展。miRNA是一类长度约20~24nt的非编码调控单链小分子RNA,其功能和作用是近年来分子生物学界关注的重点。这些微小的RNA控制着包括细胞增殖、凋亡、器官发生、发育、造血以及肿瘤发生等若干途径。最近研究发现,miRNA可能同时具有肿瘤抑制因子和源癌基因的功能,并且可能在癌症的诊断和治疗中发挥重要的作用。miRNA可以通过影响或者调控细胞增殖、分化过程中的信使RNA和关键蛋白质等参与细胞的发育。此外,miRNA对多种植物激素的调控作用对于植物体的发育也具有重要意义。     

MicroRNA调控造血干细胞发育

造血干细胞是目前研究最为深入的成体干细胞,是极富应用前景的研究领域,然而其维持自我更新以及多向分化潜能的分子机制尚不明.MicroRNA (miRNA)是一类崭新的调控性非编码小分子RNA,在监控生物体个体发育和细胞增殖、分化进程中起着重要作用.miRNA参与包括胚胎干细胞和多种成体干细胞的发育进程,人类造血干细胞及其发育过程中也存在特征性miRNA表达谱,参与调控造血干细胞发育进程,以miRNA为分子靶点的防治造血功能低下疾患的研究具有广阔的应用前景.     

MicroRNAs regulate dendritic cell differentiation and function

MicroRNAs (miRNAs) are an important class of cellular regulators that modulate gene expression and thereby influence cell fate and function. In the immune system, miRNAs act at checkpoints during hematopoietic development and cell subset differentiation, they modulate effector cell function, and they are implicated in the maintenance of homeostasis. Dendritic cells (DCs), the professional APCs involved in the coordination of adaptive immune responses, are also regulated by miRNAs. Some DC-relevant miRNAs, including miR-155 and miR-146a, are shared with other immune cells, whereas others have been newly identified. In this review, we summarize the current understanding of where miRNAs are active during DC development from myeloid precursors and differentiation into specialized subsets, and which miRNAs play roles in DC function.     

MicroRNA-148/152 impair innate response and antigen presentation of TLR-triggered dendritic cells by targeting CaMKIIα

MicroRNAs (miRNAs) are involved in the regulation of immunity, including the lymphocyte development and differentiation, and inflammatory cytokine production. Dendritic cells (DCs) play important roles in linking innate and adaptive immune responses. However, few miRNAs have been found to regulate the innate response and APC function of DCs to date. Calcium/calmodulin-dependent protein kinase II (CaMKII), a major downstream effector of calcium (Ca(2+)), has been shown to be an important regulator of the maturation and function of DCs. Our previous study showed that CaMKIIα could promote TLR-triggered production of proinflammatory cytokines and type I IFN. Inspired by the observations that dicer mutant Drosophila display defect in endogenous miRNA generation and higher CaMKII expression, we wondered whether miRNAs can regulate the innate response and APC function of DCs by targeting CaMKIIα. By predicting with software and confirming with functional experiments, we demonstrate that three members of the miRNA (miR)-148 family, miR-148a, miR-148b, and miR-152, are negative regulators of the innate response and Ag-presenting capacity of DCs. miR-148/152 expression was upregulated, whereas CaMKIIα expression was downregulated in DCs on maturation and activation induced by TLR3, TLR4, and TLR9 agonists. We showed that miR-148/152 in turn inhibited the production of cytokines including IL-12, IL-6, TNF-α, and IFN-β upregulation of MHC class II expression and DC-initiated Ag-specific T cell proliferation by targeting CaMKIIα. Therefore, miRNA-148/152 can act as fine-tuner in regulating the innate response and Ag-presenting capacity of DCs, which may contribute to the immune homeostasis and immune regulation.     

MicroRNA 对获得性免疫的调节作用

微RNA(MicroRNA,miRNA)是一类在转录后水平调节基因表达的大约22 nt的非编 码内源单链RNA.已经表明,它们与许多重要的生理和病理过程相关,包括发育、分化、细胞 凋亡、脂肪代谢、病毒感染和癌症.越来越多的证据表明,miRNA参与了获得性免疫的调节. 有趣的是,不同于开关式的调节,miRNA表现出定量的基因调节,它们能精细调节细胞免疫 反应以响应外界刺激.深入理解miRNAs对获得性免疫的调节作用有助于调节宿主免疫应答和 保护感染组织间的平衡,鉴定免疫调节新靶标和开发基于miRNA的有效疗法.本文综述了miRN A包括病毒miRNA对获得性免疫的调节作用,特别是miRNA在调节免疫活性细胞、T细胞功 能和抗体产生中的作用.     

Functional regulation of monocyte-derived dendritic cells by microRNAs

Dendritic cells (DCs) as a rare type of leukocytes play an important role in bridging the innate and adaptive immune system. A subset of DCs, monocyte-derived dendritic cells (moDCs), exists in very low numbers at steady state but become abundant in inflammatory states. These inflammation-associated DCs are potent producers of pro-inflammatory cytokines and potent inducers of T helper differentiation. They behave as a “double-edge” sword so that they not only mediate protective immunity but also immuno-pathology. It is still incompletely understood how their function is regulated. Emerging evidence indicates that microRNAs (miRNAs), as a new class of gene regulators, potently regulate the function of moDCs. Here we summarize recent progress in this area.     

Toll样受体与树突状细胞介导的天然免疫和获得性免疫

树突状细胞(dendritic cells,DCs)作为迄今所发现的抗原提呈功能最强的一类抗原提呈细胞,是联结天然免疫和获得性免疫的桥梁。Toll样受体(Toll-like receptors,TLRs)是一类进化保守的胚系编码的模式识别受体,在DCs的抗原识别、递呈及激活T细胞等方面具有重要作用,是机体受外来抗原入侵后作出适当免疫反应的调控点。现就TLRs在不同DCs亚群中的分布、与DCs介导的天然免疫和获得性免疫的关系及DCs功能可塑性的分子基础作一综述。     

microRNAs在肿瘤免疫中的调控作用

microRNAs（miRNAs）是一类转录后调控基因表达的内源性非编码微小RNA。愈来愈多的研究显示,miRNAs在肿瘤免疫应答中发挥重要调控作用。一方面,miRNAs通过转录后调控ICAM（intercellular adhesion molecule）、B7（CD80／86）和HLA—G（human leucocyte antigen—G）等肿瘤表面分子的表达,影响肿瘤的免疫原性;另一方面,miRNAs通过平衡肿瘤局部的细胞因子微环境或调控肿瘤免疫相关细胞的分化、发育及功能发挥,调节机体抗肿瘤免疫应答。为后续深入研究肿瘤与宿主的相互作用机制,以及发展更有效的肿瘤生物治疗手段,就目前miRNAs在肿瘤免疫中的调控作用的研究进展做一综述。     

昆虫miRNA研究进展

微小RNA(microRNA, miRNA)广泛存在于不同的生物体内,是一类长度为19~24 nt的内源性单链非编码小RNA,主要通过其种子区域与靶基因的开放阅读框(open reading frame, ORF)和3′非翻译区(untranslated region, UTR)进行结合,进而在转录后水平调控基因表达,miRNA在细胞分化、增殖、凋亡等多种生物学过程中均起着重要作用。随着miRNA逐渐成为生命科学研究的热点,其在昆虫中的研究也不断深入并取得了较大进展,高通量测序技术以及生物信息学的发展加快了各个物种中miRNA的鉴定,为后续miRNA相关研究提供了理论基础。直接克隆、生物信息学预测以及高通量测序都可以对不同物种中的miRNA进行鉴定,并通过miRNA基因芯片分析、Northern blot及实时荧光定量PCR(RT qPCR)检测miRNA表达水平,对其进行抑制表达或过表达可以进一步揭示miRNA的生物功能。miRNA通过参与蜕皮激素通路及调节蜕皮激素受体、性别分化、翅发育、脂质代谢和卵巢发育等相关基因的表达对昆虫的生长发育和生殖过程产生重要影响。某些昆虫的昼夜节律、记忆形成、学习能力等行为过程也不乏miRNA参与。在病毒与昆虫互作过程中,一些病毒编码的miRNA通过调节宿主基因表达,干扰宿主昆虫对病毒的免疫反应,而昆虫编码的miRNA则可以影响病毒复制。昆虫miRNA也可以通过调节自身免疫相关基因的表达,影响其先天免疫功能,在昆虫对外源病原物的免疫反应中发挥重要作用。此外,昆虫miRNA通过负向调控解毒相关基因的表达而形成或增强杀虫剂抗性,改变对农药的敏感性,在昆虫抗药性中发挥作用。本综述为进一步了解昆虫miRNA提供了理论基础,也为其在害虫综合治理中的应用提供依据。     

IL-10-conditioned dendritic cells, decommissioned for recruitment of adaptive immunity, elicit innate inflammatory gene products in response to danger signals

Dendritic cells (DCs) are the professional APCs of the immune system, enabling T cells to perceive and respond appropriately to potentially dangerous microbes, while also being able to maintain T cell tolerance toward self. In part, such tolerance can be determined by IL-10 released from certain types of regulatory T cells. IL-10 has previously been shown to render DCs unable to activate T cells and it has been assumed that this process represents a general block in maturation. Using serial analysis of gene expression, we show that IL-10 pretreatment of murine bone marrow-derived DCs alone causes significant changes in gene expression. Furthermore, these cells retain the ability to respond to Toll-like receptor agonists, but in a manner skewed toward the selective induction of mediators known to enhance local inflammation and innate immunity, among which we highlight a novel CXCR2 ligand, DC inflammatory protein-1. These data suggest that, while the presence of a protolerogenic and purportedly anti-inflammatory agent such as IL-10 precludes DCs from acquiring their potential as initiators of adaptive immunity, their ability to act as initiators of innate immunity in response to Toll-like receptor signaling is enhanced.