MicroRNAs as oncogenes

MicroRNAs (miRNAs) are a class of non-coding RNAs that function as endogenous triggers of the RNA interference pathway. Originally discovered in Caenorhabditis elegans, this group of tiny RNAs has moved to the forefront of biology. With over 300 miRNA genes identified in the human genome, and a plethora of predicted mRNA targets, it is believed that these small RNAs have a central role in diverse cellular and developmental processes. Concordant with this, aberrant expression of miRNA genes could lead to human disease, including cancer. Although the connection of miRNAs with cancer has been suspected for several years, four recent studies have confirmed the suspicion that miRNAs regulate cell proliferation and apoptosis, and play a role in cancer.     

MicroRNAs as gatekeepers of apoptosis

Apoptosis is a well‐orchestrated cellular mechanism that balances the effects of cell proliferation and cell death. MicroRNAs (miRNAs) have been shown to control cell growth, differentiation, and apoptosis; and can be significantly deregulated in many cancers types. In fact, the ability to evade apoptosis is a hallmark of tumorigenesis. Although the role of miRNAs in the regulation of apoptosis is not fully understood, the recent influx of data strongly suggests that miRNAs play a significant role in regulating programmed cell death, or apoptosis. The genes involved in apoptotic pathways can be broadly classified as pro‐apoptotic and anti‐apoptotic. Many of these apoptotic genes, irrespective of their positive or negative functional role in apoptosis, are regulated by miRNAs. In this review, we discuss the emerging role of miRNA‐mediated gene networks in the control of apoptosis. J. Cell. Physiol. 223: 289–298, 2010. © 2010 Wiley‐Liss, Inc.     

microRNA作为传染性疾病标志物的研究进展

传染性疾病往往具有较大的传染性,易于大面积流行,且难以控制,严重危害人们生命健康,快速准确的筛查成为预防及控制其传播的重要手段之一。Micro RNA(mi RNA)是一类长度仅有约22nt的非编码单链微小RNA,广泛存在于动植物真核细胞中,主要通过与靶m RNA分子的3'端非编码区域(3'-untranslated region,3'UTR)完全或不完全互补配对,调控该m RNA分子的表达或转录后翻译;在细胞生长、发育、凋亡,肿瘤形成,病毒感染等多种生理病理过程中起重要作用。在病毒感染时,mi RNA调控病毒与宿主之间的相互作用,影响病毒感染的进程与结局;感兴趣的是,mi RNA其自身的表达对病毒感染具有一定的特异性。因此,mi RNA有望成为筛查病毒传染性疾病的临床标志物,目前已成为一热点研究领域。本文主要从循环体液中mi RNA的稳定性,mi RNA在病毒感染中的特异性表达,以及mi RNA检测技术方面做简要综述,并对mi RNA作为传染病一种新型检测标志物的可行性进行了初步的分析。     

MicroRNAs Act as Cofactors in Bicoid-Mediated Translational Repression

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MicroRNAs as biomarkers and perspectives in the therapy of pancreatic cancer

Molecular and Cellular Biochemistry - Pancreatic cancer is considered as one of the most aggressive tumor types, representing over 45,750 mortality cases annually in the USA solely. The aggressive...     

Rare Circulating MicroRNAs as Biomarkers of Colorectal Neoplasia

Background

MicroRNAs (miRNAs) are regulatory RNAs, stable in circulation, and implicated in colorectal cancer (CRC) etiology and progression. Therefore they are promising as early detection biomarkers of colorectal neoplasia. However, many circulating miRNAs are highly expressed in blood cells, and therefore may not be specific to colorectal neoplasia.

Methods

We selected 7 miRNA candidates with previously reported elevated expression in adenoma tissue but low expression in blood cells (“rare” miRNAs), 2 previously proposed as adenoma biomarkers, and 3 implicated in CRC. We conducted a colonoscopy-based case-control study including 48 polyp-free controls, 43 advanced adenomas, 73 non-advanced adenomas, and 8 CRC cases. miRNAs from plasma were quantified by qRT-PCR. Correlations between miRNA expression levels, adjusted for age and sex, were assessed. We used polytomous logistic regression to estimate odds ratios (ORs) and 95% confidence intervals quantifying the association between expression levels of miRNAs and case groups. We also conducted nonparametric receiver operating characteristic (ROC) analyses and estimated area under the curve (AUC).

Results

miRNAs with high expression levels were statistically significantly correlated with one another. No miRNAs were significantly associated with non-advanced or advanced adenomas. Strong (ORs >5) and significant associations with CRC were observed for 6 miRNA candidates, with corresponding AUCs significantly >0.5.

Conclusions

These candidate miRNAs, assayed by qRT-PCR, are probably unsuitable as blood-based adenoma biomarkers. Strong associations between miRNAs and CRC were observed, but primarily with miRNAs highly expressed in blood cells. These results suggest that rare miRNAs will require new detection methods to serve as circulating biomarkers of adenomas.     

MicroRNAs as a therapeutic target for cardiovascular diseases

MicroRNAs (miRNAs) are tiny, endogenous, conserved, non-coding RNAs that negatively modulate gene expression by either promoting the degradation of mRNA or down-regulating the protein production by translational repression. They maintain optimal dose of cellular proteins and thus play a crucial role in the regulation of biological functions. Recent discovery of miRNAs in the heart and their differential expressions in pathological conditions provide glimpses of undiscovered regulatory mechanisms underlying cardiovascular diseases. Nearly 50 miRNAs are overexpressed in mouse heart. The implication of several miRNAs in cardiovascular diseases has been well documented such as miRNA-1 in arrhythmia, miRNA-29 in cardiac fibrosis, miRNA-126 in angiogenesis and miRNA-133 in cardiac hypertrophy. Aberrant expression of Dicer (an enzyme required for maturation of all miRNAs) during heart failure indicates its direct involvement in the regulation of cardiac diseases. MiRNAs and Dicer provide a particular layer of network of precise gene regulation in heart and vascular tissues in a spatiotemporal manner suggesting their implications as a powerful intervention tool for therapy. The combined strategy of manipulating miRNAs in stem cells for their target directed differentiation and optimizing the mode of delivery of miRNAs to the desired cells would determine the future potential of miRNAs to treat a disease. This review embodies the recent progress made in microRNomics of cardiovascular diseases and the future of miRNAs as a potential therapeutic target - the putative challenges and the approaches to deal with it.     

MicroRNAs as genetic sculptors: Fishing for clues

microRNAs (miRNAs) encode small RNA molecules of ～22nts in length that regulate the deadenylation, translation, and decay of their target mRNAs. The identification of miRNAs in plants and animals has uncovered a new layer of gene regulation with important implications for development, cellular homeostasis and disease. Because each miRNA is predicted to regulate several hundred genes, a major challenge in the field remains to elucidate the precise roles for each miRNA and to understand the physiological relevance of individual miRNA–target interactions in vivo. Despite the wide variety of biological contexts where miRNAs function, a common theme emerges, whereby miRNAs shape gene expression within both spatial and temporal dimensions by removing messages from previous cellular states as well as modulating the levels of actively transcribed genes. This review will focus on the role that the teleost Danio rerio (zebrafish) has played in shaping our understanding of miRNA function in vertebrates.     

MicroRNAs as potential investigative and predictive biomarkers in colorectal cancer

Colorectal cancer (CRC) is a noticeable reason of cancer-associated deaths with a high incidence and mortality rate. Countless effort have been put into the improving clinical management of CRC patients including more effective tools and a wide variety of biomarkers for diagnostic, prognostic or predictive purposes. In recent years, dysregulated miRNAs have been emerged as highly sensitive and specific markers to manage CRC in an effective way. They can play key roles in carcinogenesis as potential oncogenes, tumor suppressors or regulators of cancer network. Therefore, miRNAs may serve as molecular tools that can be quantified and used in diagnostic and prognostic approaches. Growing evidence also suggests that forced expression of tumor suppressor miRNAs or inhibiting the oncogene ones, can be used as a novel treatment strategy. In this review, we focus on the clinical applications of miRNAs as promising biomarkers of early cancer detection, prognosis and treatment.     

Anopheles gambiae miRNAs as actors of defence reaction against Plasmodium invasion

The path Plasmodium takes across the Anopheles midgut constitutes the major bottleneck during the malaria transmission cycle. In the present study, using a combination of shot-gun cloning and bioinformatic analysis, we have identified 18 miRNAs from Anopheles gambiae including three miRNAs unique to mosquito. Twelve of them are expressed ubiquitously across the body, independently of gender, while the other six exhibited an expression pattern restricted to the digestive system. Strikingly, the expression patterns of four miRNAs, including the three unique to mosquito, are affected by the presence of Plasmodium. We also show that knocking down Dicer1 and Ago1 mRNAs led to an increased sensitivity to Plasmodium infection. Altogether, these data support an involvement of miRNAs as new layers in the regulation of Anopheles defence reaction.