MicroRNA调控机制及在脂肪形成中的作用

MicroRNA(miRNA)是近几年发现的一类通过转录后调控机制对基因进行调控的非编码的短链RNA,广泛存在于真核生物。miRNAs在个体时序性发育、细胞增殖分化和凋亡、器官发育、脂肪代谢等许多生物发育过程中起着重要作用,并与肿瘤等疾病发生发展密切相关。近年来对miRNA的研究证实,大量miRNA参与脂肪组织发育相关的许多生物学过程调控。主要涉及miRNA的生物合成、调控靶基因转录后表达的机制(如降解mRNA序列、阻断翻译起始、处理小体转位及翻译激活),及其在脂肪形成中的作用,以期为更好地理解miRNA在脂肪形成中的作用,深入研究脂肪形成的分子机制提供参考。     

microRNA生物合成的调控进展——TGFβ/Smad信号途径的作用

microRNA（miRNA）是一类非编码的小分子单链RNA,主要通过转录后抑制靶基因表达调节各种生物功能。miRNA表达水平在正常发育过程中以及在癌症及心血管疾病等各种疾病中发生变化。目前控制miRNA生物合成的信号途径以及调节机制尚未完全阐明。miRNA基因转录后在大蛋白复合体的介导下经一系列协调加工过程形成成熟的miRNA。近来发现转化生长因子β（TGFβ）信号途径的转导因子Smad蛋白在细胞核内调节miRNA的加工处理过程起重要作用。本文主要综述TGFβ/Smad信号途径在miRNA生物合成中的调节作用。     

microRNA 生物合成的调控进展--TGFβ/Smad 信号途径的作用

microRNA(miRNA)是一类非编码的小分子单链RNA,主要通过转录后抑制靶基因表达调节各种生物功能.miRNA表达水平在正常发育过程中以及在癌症及心血管疾病等各种疾病中发生变化.目前控制miRNA生物合成的信号途径以及调节机制尚未完全阐明.miRNA基因转录后在大蛋白复合体的介导下经一系列协调加工过程形成成熟的miRNA.近来发现转化生长因子B(TGFβ)信号途径的转导因子Smad蛋白在细胞核内调节miRNA的加工处理过程起重要作用.本文主要综述TGFB/Smad信号途径在miRNA生物合成中的调节作用.     

模式生物与microRNA研究

microRNA（miRNA）是一类内源性、长度在19~25个碱基的小分子非编码RNA,其在基因的转录后调控中发挥重要功能.miRNA的研究在最近得到了快速发展,模式生物在这一过程中起到了重要作用.本文介绍了不同模式生物在miRNA的发现、作用机制和生物学功能研究中的作用.     

MicroRNAs与疾病和发育

作为模式生物实验系统,线虫可用于研究控制动物发育和人类疾病遗传机制。研究发育缺陷的线虫突变体有助于在动物中发现对发育和生理过程有重要调控作用的基因。其中一些基因编码一类小RNA,如microRNA(miRNA),通过作用于特定基因信使RNA来调控其蛋白质表达。一些在线虫发育过程中有功能的miRNA在人体中也存在。它们参与调控与疾病相关的生物学过程,如癌症、糖尿病和神经退行性疾病。通过分析miRNA在临床样品、哺乳动物细胞和模式生物线虫中的表达,从而揭示miRNA调控途径在相关人类疾病中的功能。     

植物miRNA的分子特征及其在逆境中的响应机制

逆境胁迫是影响植物生长发育、生物产量与品质形成的主要因素之一。通过诱导表达抗逆有关的编码基因与部分非编码基因是植物响应逆境的主要方式。miRNA作为一种非编码基因在植物生长、发育以及抗逆等过程中起重要的调控作用。研究表明:逆境胁迫下miRNA可以形成miRNA诱导沉默复合物(miRNA-induced silencing complex,miRISC),并与靶mRNA互补配对结合,进而引起靶mRNA的降解或者抑制其翻译,从而实现对下游抗逆相关基因表达的调控,最终引起代谢与信号转导途径的变化实现对逆境的响应。本文从植物逆境胁迫下诱导miRNA的产生、靶基因的识别以及作用机制等方面进行了综述。     

microRNAs在肝细胞癌中的调控机制及临床应用

microRNA（miRNA）在人类恶性肿瘤的发生发展过程中起着重要作用。近期研究表明,miRNA通过结合特定靶标参与调控肝细胞癌（hepatocellularcarcinoma,HCC）的发生,可作为辅助生物标志物用于指导肝细胞癌的诊断和治疗,并为有效地监控和预防肝病提供了新途径。寻找miRNA靶标,阐明miRNA参与肝癌发生的调控机理,有利于肝癌的临床靶向基因治疗。通过总结miRNA在肝细胞癌中的调控机制及临床应用的研究进展,为寻找肝细胞癌早期诊断的生物标志物及介入治疗的靶点提供了参考。     

miRNA调控昆虫与病毒互作的研究进展

miRNA是一类重要的非编码小分子RNA,可在转录后水平调控基因表达,参与并调控机体的生长发育、细胞分化、细胞凋亡、抗病毒、激素分泌、神经系统等重要生物过程。本文介绍了miRNA的合成途径及其生物学功能,并重点阐述miRNA在昆虫宿主与病毒互作中的调控作用:通过mRNA剪切或抑制靶标蛋白的翻译负调控靶标基因,实现基因沉默,调控约50%的蛋白质编码基因的表达,许多miRNA已被发现在人体和植物中参与调控病毒的复制侵染,因此也有可能控制害虫对病毒抗性的产生,恢复病毒对害虫的防控作用。最近有研究将害虫特异的miRNA转入植物,干扰昆虫蜕皮过程导致幼虫的死亡,作为Bt转基因作物的替代,成为抗虫基因工程的新选择。研究miRNA在昆虫对病毒抗性产生中的作用,将为昆虫抗病毒机制的研究提供新的思路,为害虫生物防治措施的应用及改进提供理论参考。     

植物MicroRNA

MicroRNA (miRNA)是一类长度约为22个核苷酸的内源单链非编码RNA,在结构上相当保守,因而可以借助生物信息学方法进行预测. 从2002年证实miRNA在植物中的存在以来,关于植物miRNA的研究进展异常迅速,短短几年内就已发现200多种. 植物miRNA主要通过切割靶mRNA,或抑制靶mRNA翻译,来调控植物个体生长发育并影响其生理过程,是一种新的基因调控方式. 本文将就植物miRNA的形成、特征、作用机制、生物功能及其与siRNA的关系进行综述.     

猪microRNA组学研究进展

MicroRNA(miRNA)是一类长约22 nt的非编码小RNA,广泛存在于各种生物中,调节生物体生长、发育和凋亡等过程。研究表明,miRNA在猪肌肉、脂肪、生殖系统以及免疫系统等的发育过程中发挥着重要的调控作用。此外,高通量的新一代测序技术在猪miRNA的挖掘和差异表达研究中发挥着巨大的作用。文章综述了高通量的新一代测序技术在挖掘猪miRNA中的应用以及一些miRNA在猪脂肪代谢、肌肉发育、卵母细胞成熟和B、T淋巴细胞发育中的调控作用,旨在为猪miRNA的研究提供参考,为利用miRNA调控和改善猪肉品质、生长性能、繁殖性能以及免疫机能提供理论基础和研究思路。     

PGC-Enriched miRNAs Control Germ Cell Development

Non-coding microRNAs (miRNAs) regulate the translation of target messenger RNAs (mRNAs) involved in the growth and development of a variety of cells, including primordial germ cells (PGCs) which play an essential role in germ cell development. However, the target mRNAs and the regulatory networks influenced by miRNAs in PGCs remain unclear. Here, we demonstrate a novel miRNAs control PGC development through targeting mRNAs involved in various cellular pathways. We reveal the PGC-enriched expression patterns of nine miRNAs, including miR-10b, -18a, -93, -106b, -126-3p, -127, -181a, -181b, and -301, using miRNA expression analysis along with mRNA microarray analysis in PGCs, embryonic gonads, and postnatal testes. These miRNAs are highly expressed in PGCs, as demonstrated by Northern blotting, miRNA in situ hybridization assay, and miRNA qPCR analysis. This integrative study utilizing mRNA microarray analysis and miRNA target prediction demonstrates the regulatory networks through which these miRNAs regulate their potential target genes during PGC development. The elucidated networks of miRNAs disclose a coordinated molecular mechanism by which these miRNAs regulate distinct cellular pathways in PGCs that determine germ cell development.     

microRNAs - powerful repression comes from small RNAs

microRNAs (miRNAs) encode a novel class of small, non-coding RNAs that regulate gene expression post-trancriptionally. miRNAs comprise one of the major non-coding RNA families, whose diverse biological functions and unusual capacity for gene regulation have attracted enormous interests in the RNA world. Over the past 16 years, genetic, biochemical and computational approaches have greatly shaped the growth of the field, leading to the identification of thousands of miRNA genes in nearly all metazoans. The key molecular machinery for miRNA biogenesis and silencing has been identified, yet the precise biochemical and regulatory mechanisms still remain elusive. However, recent findings have shed new light on how miRNAs are generated and how they function to repress gene expression. miRNAs provide a paradigm for endogenous small RNAs that mediate gene silencing at a genome-wide level. The gene silencing mediated by these small RNAs constitutes a major component of gene regulation during various developmental and physiological processes. The accumulating knowledge about their biogenesis and gene silencing mechanism will add a new dimension to our understanding about the complex gene regulatory networks.     

Inferring the perturbed microRNA regulatory networks from gene expression data using a network propagation based method

Background

MicroRNAs (miRNAs) are a class of endogenous small regulatory RNAs. Identifications of the dys-regulated or perturbed miRNAs and their key target genes are important for understanding the regulatory networks associated with the studied cellular processes. Several computational methods have been developed to infer the perturbed miRNA regulatory networks by integrating genome-wide gene expression data and sequence-based miRNA-target predictions. However, most of them only use the expression information of the miRNA direct targets, rarely considering the secondary effects of miRNA perturbation on the global gene regulatory networks.

Results

We proposed a network propagation based method to infer the perturbed miRNAs and their key target genes by integrating gene expressions and global gene regulatory network information. The method used random walk with restart in gene regulatory networks to model the network effects of the miRNA perturbation. Then, it evaluated the significance of the correlation between the network effects of the miRNA perturbation and the gene differential expression levels with a forward searching strategy. Results show that our method outperformed several compared methods in rediscovering the experimentally perturbed miRNAs in cancer cell lines. Then, we applied it on a gene expression dataset of colorectal cancer clinical patient samples and inferred the perturbed miRNA regulatory networks of colorectal cancer, including several known oncogenic or tumor-suppressive miRNAs, such as miR-17, miR-26 and miR-145.

Conclusions

Our network propagation based method takes advantage of the network effect of the miRNA perturbation on its target genes. It is a useful approach to infer the perturbed miRNAs and their key target genes associated with the studied biological processes using gene expression data.

Electronic supplementary material

The online version of this article (doi:10.1186/1471-2105-15-255) contains supplementary material, which is available to authorized users.     

Molecular mechanisms and microRNAs in osteosarcoma pathogenesis

This review summarizes data on microRNA (miRNA) genomic organization, biogenesis, and functions in carcinogenesis. The roles of key genes and regulatory miRNAs in molecular mechanisms and signaling pathways involved in the development of osteosarcoma, the most aggressive type of bone tumor striking mainly in adolescence and early adulthood, are discussed in detail. The most critical pathways in osteosarcoma pathogenesis are the Notch, Wnt, NF-κB, p53, PI3K/Akt, and MAPK pathways. The balance between cell survival and apoptosis is determined by the Wnt and NF-κB pathways, as well as by the ratio between the activities of the MAPK and PI3K/Akt pathways. Several miRNAs (miR-21, -34a, -143, -148a, -195a, -199a-3p, -382) regulate multiple target genes, pathways, and processes essential for osteosarcoma pathogenesis. Data on the key genes and regulatory miRNAs involved in metastasis and tumor cell response to drug treatment are presented. Possible applications of miRNA in osteosarcoma diagnostics and treatment are discussed.