miRNApath: a database of miRNAs, target genes and metabolic pathways

MicroRNAs (miRNAs) are small non-coding RNAs that regulate target gene expression and hence play important roles in metabolic pathways. Recent studies have evidenced the interrelation of miRNAs with cell proliferation, differentiation, development, and diseases. Since they are involved in gene regulation, they are intrinsically related to metabolic pathways. This leads to questions that are particularly interesting for investigating medical and laboratorial applications. We developed an miRNApath online database that uses miRNA target genes to link miRNAs to metabolic pathways. Currently, databases about miRNA target genes (DIANA miRGen), genomic maps (miRNAMap) and sequences (miRBase) do not provide such correlations. Additionally, miRNApath offers five search services and a download area. For each search, there is a specific type of input, which can be a list of target genes, miRNAs, or metabolic pathways, which results in different views, depending upon the input data, concerning relationships between the target genes, miRNAs and metabolic pathways. There are also internal links that lead to a deeper analysis and cross-links to other databases with more detailed information. miRNApath is being continually updated and is available at http://lgmb.fmrp.usp.br/mirnapath.     

microRNA调控棕色脂肪细胞的分化

微小RNA（microRNA,miRNA）是一类长度约为20~24个核苷酸序列的内源性的具有转录后调节功能的单链非编码小RNA,在基因表达调控方面具有广泛作用,参与了生物体生长发育、细胞增殖、分化、凋亡等多种生物学过程.最新研究发现,microRNA193b-365在棕色脂肪细胞分化过程中,通过上调或下调一些影响棕色脂肪细胞分化方向的因子（如Runx1t1 、Cdon、Igfbp5、PRDM16等）的表达水平,而发挥促进棕色脂肪细胞分化的功能.促进棕色脂肪形成可增加热量的产生,同时减少脂肪堆积,从而有助于减少肥胖症及其相关疾病的发生.microRNA正性调控棕色脂肪细胞分化这一作用机制为治疗肥胖症的研究提供了新方向,有可能成为脂类代谢性疾病治疗的潜在靶点.     

Plant-derived xenomiRs and cancer: Cross-kingdom gene regulation

Exosomal microRNAs (miRNAs) critically regulate several major intracellular and metabolic activities, including cancer evolution. Currently, increasing evidence indicates that exosome harbor and transport these miRNAs from donor cells to neighboring and distantly related recipient cells, often in a cross-species manner. Several studies have reported that plant-based miRNAs can be absorbed into the serum of humans, where they hinder the expression of human disease-related genes. Moreover, few recent studies have demonstrated the role of these xenomiRs in cancer development and progression. However, the cross-kingdom gene regulation hypothesis remains highly debatable, and many follow up studies fail to reproduce the same. There are reports that show no effect of plant-derived miRNAs on mammalian cancers. The foremost cause of this controversy remains the lack of reproducibility of the results. Here, we reassess the latest developments in the field of cross-kingdom transference of miRNAs, emphasizing on the role of the diet-based xenomiRs on cancer progression.     

Role of microRNAs in obesity and obesity-related diseases

In recent years, the link between regulatory microRNAs (miRNAs) and diseases has been the object of intensive research. miRNAs have emerged as key mediators of metabolic processes, playing crucial roles in maintaining/altering physiological processes, including energy balance and metabolic homeostasis. Altered miRNAs expression has been reported in association with obesity, both in animal and human studies. Dysregulation of miRNAs may affect the status and functions of different tissues and organs, including the adipose tissue, pancreas, liver, and muscle, possibly contributing to metabolic abnormalities associated with obesity and obesity-related diseases. More recently, the discovery of circulating miRNAs easily detectable in plasma and other body fluids has emphasized their potential as both endocrine signaling molecules and disease indicators. In this review, the status of current research on the role of miRNAs in obesity and related metabolic abnormalities is summarized and discussed.     

MicroRNAs与多潜能干细胞的研究进展

microRNAs(miRNAs)是一类内源性非编码小RNA,通过调控基因表达来参与生命过程中的一系列重要进程。越来越多的证据表明,miRNAs参与了几乎所有生物代谢过程,其胚胎干细胞的自我更新与分化和在多能干细胞(iPSCs)中的诱导调节作用也日益受到关注。该文介绍了miRNAs的生成、检测方法以及miRNAs对胚胎干细胞(ESCs)及诱导多能性干细胞的调控作用,并对miRNAs的应用前景进行了展望。     

Deep Sequencing of Small RNA Repertoires in Mice Reveals Metabolic Disorders-Associated Hepatic miRNAs

Obesity and associated metabolic disorders contribute importantly to the metabolic syndrome. On the other hand, microRNAs (miRNAs) are a class of small non-coding RNAs that repress target gene expression by inducing mRNA degradation and/or translation repression. Dysregulation of specific miRNAs in obesity may influence energy metabolism and cause insulin resistance, which leads to dyslipidemia, steatosis hepatis and type 2 diabetes. In the present study, we comprehensively analyzed and validated dysregulated miRNAs in ob/ob mouse liver, as well as miRNA groups based on miRNA gene cluster and gene family by using deep sequencing miRNA datasets. We found that over 13.8% of the total analyzed miRNAs were dysregulated, of which 37 miRNA species showed significantly differential expression. Further RT-qPCR analysis in some selected miRNAs validated the similar expression patterns observed in deep sequencing. Interestingly, we found that miRNA gene cluster and family always showed consistent dysregulation patterns in ob/ob mouse liver, although they had various enrichment levels. Functional enrichment analysis revealed the versatile physiological roles (over six signal pathways and five human diseases) of these miRNAs. Biological studies indicated that overexpression of miR-126 or inhibition of miR-24 in AML-12 cells attenuated free fatty acids-induced fat accumulation. Taken together, our data strongly suggest that obesity and metabolic disturbance are tightly associated with functional miRNAs. We also identified hepatic miRNA candidates serving as potential biomarkers for the diagnose of the metabolic syndrome.     

The involvement of microRNAs in Type 2 diabetes

T2D (Type 2 diabetes mellitus) is a major health issue that has reached epidemic status worldwide. T2D is a progressive metabolic disorder characterized by reduced insulin sensitivity, insulin resistance and pancreatic β-cell dysfunction. Improper treatment of TD2 can lead to severe complications such as heart disease, stroke, kidney failure, blindness and nerve damage. The aetiology and molecular mechanisms of T2D are not fully understood, but compelling evidence points to a link between T2D, obesity, dyslipidaemia and insulin resistance. Although T2D seems to be strongly linked to environmental factors such as nutrition and lifestyle, studies have shown that genetic factors, such as polymorphisms associated with metabolic genes, imprinting, fetal programming and miRNA (microRNA) expression, could also contribute to the development of this disease. miRNAs are small 22-25-nt-long untranslated RNAs that negatively regulate the translation of mRNAs. miRNAs are involved in a large number of biological functions such as development, metabolism, immunity and diseases such as cancer, cardiovascular diseases and diabetes. The present review examines the various miRNAs that have been identified as being potentially involved in T2D, focusing on the insulin-sensitive organs: white adipose tissue, liver, skeletal muscle and the insulin-producing pancreatic β-cells.     

微小RNA和长链非编码RNA介导的昼夜节律调控

非编码RNA(ncRNA)是生物体细胞内一类重要的调控分子,其介导的昼夜节律调控日益受到研究者的重视。本文主要以黑腹果蝇Drosophila melanogaster和哺乳动物的相关研究为背景,阐述了微小RNA(miRNA)和长链非编码RNA(lncRNA)对昼夜节律的调控。miRNA介导的昼夜节律调控包括:生物体内(尤其是钟神经元中)具有节律性表达的miRNA;输入系统和miRNA存在相互调控,这主要是通过光照这个授时因子起作用;miRNA可直接调控核心振荡器,还可以调控其他基因而间接影响到核心振荡器;miRNA对输出系统的调控主要集中在代谢取食节律、运动节律、睡眠节律等。昼夜节律可调控lncRNA的表达,同时lncRNA也可调控昼夜节律,且lncRNA对基因调控范围广,作用机制复杂,这些都具有广阔的研究前景。本文将有助于进一步深入研究ncRNA对昼夜节律的调控。     

A bioinformatics-based update on microRNAs and their targets in rainbow trout (Oncorhynchus mykiss)

MicroRNAs (miRNAs) participate in various vitally biological processes via controlling target genes activity and thousands of miRNAs have been identified in many species to date, including 18,698 known animal miRNA in miRBase. However, there are only limited studies reported in rainbow trout (Oncorhynchus mykiss) especially via the computational-based approaches. In present study, we systematically investigated the miRNAs in rainbow trout using a well-developed comparative genome-based homologue search. A total of 196 potential miRNAs, belonging to 124 miRNA families, were identified, most of which were firstly reported in rainbow trout. The length of miRNAs ranged from 17 to 24 nt with an average of 20 nt while the length of their precursors varied from 47 to 152 nt with an average of 85 nt. The identified miRNAs were not evenly distributed in each miRNA family, with only one member per family for a majority, and multiple members were also identified for several families. Nucleotide U was dominant in the pre-miRNAs with a percentage of 30.04%. The rainbow trout pre-miRNAs had relatively high negative minimal folding free energy (MFE) and adjusted MFE (AMFE). Not only the mature miRNAs but their precursor sequences are conserved among the living organisms. About 2466 O. mykiss genes were predicted as potential targets for 189 miRNAs. Gene Ontology (GO) analysis showed that nearly 2093, 2107, and 2081 target genes are involved in cellular component, molecular function, and biological processes respectively. KEGG pathway enrichment analysis illuminated that these miRNAs targets might regulate 105 metabolic pathways, including those of purine metabolism, nitrogen metabolism, and oxidative phosphorylation. This study has provided an update on rainbow trout miRNAs and their targets, which represents a foundation for future studies.     

脂肪组织中的miRNAs研究进展

miRNA是近年来发现的一类长约22 nt的内源性非编码RNA,在动物中主要通过抑制靶mRNA翻译,在转录后水平调控基因表达。大量研究表明脂肪组织中的miRNAs参与了脂肪细胞分化、脂代谢等多种生物过程调控,其自身也受到转录因子、脂肪细胞因子和环境因子等调控,这些复杂的相互作用关系构成了脂肪组织中miRNA的调控网络,循环miRNA的发现为这个网络加入了新元素。对肥胖等代谢疾病的研究,应该从这个复杂的动态网络中寻找答案。文中综述了脂肪组织中miRNA的最新研究进展,以期为利用miRNA进行肥胖等相关代谢失调疾病的治疗提供新思路。     

MicroRNAs: Emerging roles in adipogenesis and obesity

Obesity is a serious health problem worldwide associated with an increased risk of life-threatening diseases such as type 2 diabetes, atherosclerosis, and certain types of cancer. Understanding the molecular basis of adipogenesis and fat cell development in obesity is essential to identify new biomarkers and therapeutic targets for the development of anti-obesity drugs. Recent computational and experimental studies have shown that microRNAs (miRNAs) appear to play regulatory roles in many biological processes associated with obesity, including adipocyte differentiation and lipid metabolism. In addition, many miRNAs are dysregulated in metabolic tissues from obese animals and humans, which potentially contributes to the pathogenesis of obesity-associated complications. The discovery of circulating miRNAs has highlighted their potential as both endocrine signaling molecules and disease markers. The potential of miRNA based therapeutics targeting obesity is highlighted as well as recommendations for future research which could lead to a breakthrough in the treatment of obesity.