oalib
Search Results: 1 - 10 of 100 matches for " "
All listed articles are free for downloading (OA Articles)
Page 1 /100
Display every page Item
Circulating MicroRNAs: Potential Biomarkers for Cancer  [PDF]
De-Cai Yu,Qing-Guo Li,Xi-Wei Ding,Yi-Tao Ding
International Journal of Molecular Sciences , 2011, DOI: 10.3390/ijms12032055
Abstract: Cancer is the leading cause of death in the world. Development of minimally invasive biomarkers for early detection of cancer is urgently needed to reduce high morbidity and mortality associated with malignancy. MicroRNAs (miRNAs) are small regulatory RNAs that modulate the activity of specific mRNA targets and play important roles in a wide range of physiologic and pathologic processes. Recently, miRNAs were found to be dysregulated in a variety of diseases including cancer. Emerging evidence suggests that miRNAs are involved in tumor initiation and progression. Together, the different expression profiles of miRNAs in cancer, and the stability of circulating miRNAs, make them new potentially clinical biomarkers for cancer diagnosis, classification, therapeutic decisions, and prognosis.
MicroRNAs as Potential Biomarkers in Acute Promyelocytic Leukaemia  [PDF]
Imilia Ismail,Sarina Sulong,Rosline Hassan
New Journal of Science , 2014, DOI: 10.1155/2014/932342
Abstract: Acute promyelocytic leukaemia (APL) is an M3 subtype of acute myeloid leukaemia (AML). This classification is based on the morphology of promyelocytic cell. The clinical characteristics of APL can be recognized by haemorrhagic episodes, a differentiation block at the promyelocytic stage, and sensitivity to the differentiation response to all-trans-retinoic acid (ATRA). Cytogenetically, APL is characterized by a balanced reciprocal translocation between chromosomes 15 and 17, which results in the production of PML/RARα fusion protein. Recent studies reported that microRNAs (miRNAs) have also been proposed to contribute to the pathogenesis of APL. miRNAs have been associated with the pathogenesis of cancer and their involvement as oncogenic and tumour suppressor activities have been identified. They are involved in various biological processes including the cell proliferation, differentiation, growth and development, metabolism, apoptosis, and haematopoiesis. The new discovery of miRNAs as possible therapeutic markers will provide new insight for the diagnosis and therapeutic entries for the treatment of APL. This review highlights the potential of miRNAs as biomarkers in APL. 1. Introduction Acute promyelocytic leukaemia (APL) is identified as the M3 subtype of acute myeloid leukaemia (AML) by the French-American-British (FAB) classification. This classification is based on the percentage of maturing cells beyond the myeloblast stage. Bone marrow shows hypercellular promyelocytes and the most striking feature of these cells is the cytoplasmic hypergranularity. Multiple Auer rods are also observed in a few early cells in APL. According to WHO 2008 classification, APL is characterized by a reciprocal translocation between chromosomes 15 and 17, which results in the fusion between the promyelocytic leukaemia (PML) gene and retinoic acid receptor α (RARα) gene [1]. A schematic representation of the chromosomes and genes involved in t(15;17) is shown in Figure 1. Figure 1: Chromosomal reciprocal translocation of the 15th and 17th chromosomes. The breakpoints on chromosome 17 are consistently located within the second intron of the RARα gene, but, on chromosome 15, there are different breakpoint cluster regions, namely bcr1, bcr2, and bcr3 located in intron 6, exon 6, and intron 3, respectively, of the PML gene [2, 3]. The location of bcr1, bcr2, and bcr3 produces fusion transcripts of varying lengths referred to as the long, variant, and short forms, respectively [3]. This translocation can be detected by karyotyping or fluorescence in situ hybridization
Circulating microRNAs: A Potential Role in Diagnosis and Prognosis of Acute Myocardial Infarction  [PDF]
Ali Sheikh Md Sayed,Ke Xia,Tian-Lun Yang,Jun Peng
Disease Markers , 2013, DOI: 10.1155/2013/217948
Abstract: Rapid and correct diagnosis of acute myocardial infarction (AMI) plays a crucial role in saving patients' life. Although some biomarkers (such as cardiac troponin and creatine kinase) are available for AMI diagnosis so far, there is still a clinical need for novel biomarkers, which can reliably rule in or rule out AMI immediately on admission. Circulating microRNAs (miRNAs) are a potential choice for novel biomarkers in AMI diagnosis and prognosis with high sensitivity and specificity. Circulating microRNAs are endogenous miRNAs that are detectable in whole blood, serum, or plasma in a highly stable form. Until now, around 20 circulating miRNAs were reported to be closely associated with AMI. In this minireview, we summarized recent available data on the correlation between circulating miRNAs and AMI. Some miRNAs, such as miR-208, miR-499, miR-133, and miR-1, were given special attention, since they may have a potential prospect in diagnosis and prognosis of AMI. 1. Introduction Coronary artery disease (CAD) is a very common health problem in the developed as well as developing countries. Acute myocardial infarction (AMI) is one of the leading causes for death worldwide, and it is the single largest cause of death in the United States, responsible for 1 out of every 6 deaths [1, 2]. Rapid and correct diagnosis of AMI plays an important role in therapy and prognosis for this disease. Over the past two decades, huge progress has been made in the diagnosis, treatment, and prognosis of AMI. Particularly, the progress in biomarkers for AMI attracted a great deal of attention. Currently, cardiac troponins are the most common biomarkers used for diagnosis of AMI in clinical practice. However, there is still a clinical need for novel biomarker, which is able to reliably rule in or rule out AMI immediately on admission. MicroRNAs (miRNAs) seem to be a promising candidate of novel biomarker for early diagnosis of AMI [3]. In the last few years, the dysregulation of tissue expression levels of miRNAs has been directly linked to cardiac disease. In addition to expression changes in tissues, more recent studies have indicated that miRNAs are detectable in serum, plasma, urine, and other body fluids in a highly stable form that is protected from endogenous RNase activity [4]. Altered circulating miRNA concentrations have been detected in patients with AMI [5], acute coronary syndrome (ACS) [6], stable coronary artery disease [7], heart failure [8], coronary atherosclerosis, cardiac arrhythmia, cardiomyopathy, and cardiac hypertrophy [9]. This review will focus on a
MicroRNAs in diabetic cardiomyopathy and clinical perspectives  [PDF]
Qiulian Zhou,Ping Chen,Siyi Fu,Jin Li,Yihua BEI
Frontiers in Genetics , 2014, DOI: 10.3389/fgene.2014.00185
Abstract: Diabetes is a progressive metabolic disorder that can ultimately lead to serious chronic vascular complications including renal failure, vision loss and cardiac dysfunction (Ruiz and Chakrabarti, 2013). Diabetic cardiomyopathy is responsible for higher incidence of sudden cardiac death and represents the leading cause of morbidity and mortality among the diabetic patients (Aksnes et al., 2007; Chavali et al., 2013). Previous studies have indicated that oxidative stress and mitochondrial dysfunction were critically involved in the etiology of diabetes-induced cardiac dysfunction (Styskal et al., 2012; Sugamura and Keaney, 2011), that could subsequently induce a cascade of complex pathophysiological events characterized by early impairments of diastolic function, development of cardiomyocyte hypertrophy, myocardial fibrosis and cardiomyocyte apoptosis, eventually leading to heart failure (Huynh et al., 2014). However, the underlying mechanisms of diabetic cardiomyopathy are far from understood and current therapeutic strategies do not specifically aim at diabetic cardiomyopathy and diabetes-induced heart failure. MicroRNAs (miRNAs, miRs), a novel class of non-coding RNAs of 22~24 nucleotides in length, act as post-transcriptional regulators of gene expression by binding to the 3’-untranslated region (3’-UTR) of target mRNA that induces mRNA degradation and/or translational repression (van Rooij, 2011; Lim et al., 2005). Given that miRNAs are crucially involved in many critical biological processes including cell proliferation, apoptosis, necrosis, migration and differentiation (Bartel, 2004), desregulated miRNAs contribute to many human diseases including diabetes (McClelland and Kantharidis, 2014; Tyagi et al., 2011; Shantikumar et al., 2012) and cardiovascular diseases (Xiao et al., 2012; Fu et al., 2013; Vickers et al., 2014). Recent studies demonstrate that aberrant expression of miRNAs also participates in the pathogenetic processes mediating diabetic cardiomyopathy, where miR-1, -133, -141, -206, -223 have been reported upregulated, whereas miR-133a, -373 and -499 downregulated (Asrih and Steffens, 2013; Shantikumar et al., 2012; Shen et al., 2011). Thus it is of crucial importance to gain insight into the role of miRNAs in the development of diabetic cardiomyopathy which will help clarify the molecular mechanisms as well as identify novel therapeutic strategies for diabetic cardiomyopathy. Cardiomyocyte hypertrophy, myocardial fibrosis and cardiomyocyte apoptosis are important features of diabetic cardiomyopathy (Ruiz and Chakrabarti, 2013).
MicroRNAs: The Potential Biomarkers in Plant Stress Response  [PDF]
Sonali Bej, Jolly Basak
American Journal of Plant Sciences (AJPS) , 2014, DOI: 10.4236/ajps.2014.55089
Abstract:

MicroRNAs (miRNAs) are endogenous small RNA regulatory molecules of approximate 20-24 nucleotides that are involved in regulating the intrinsic growth and development of organs in plants and animals as well as in maintaining the integrity of genomes. Past few years have witnessed an increase in research reports on the crucial role of miRNAs in plant stress response. Plant miRNAs regulate gene expression at the post-transcriptional level not only by suppression of mRNA translation but also by direct cleavage of the target mRNAs. This review starts with a brief overview on small RNAs including miRNAs, biogenesis of miRNA and focuses mainly on the various up and down-regulated plant miRNAs under different biotic and abiotic stresses showing advancement of studies about miRNA and their stress regulation pathway. This review explores the emerging role of miRNAs as potential biomarkers in plant stress responses.

Microprocessor of microRNAs: regulation and potential for therapeutic intervention
Kevin J Beezhold, Vince Castranova, Fei Chen
Molecular Cancer , 2010, DOI: 10.1186/1476-4598-9-134
Abstract: MicroRNAs (miRNAs) are endogenously synthesized small non-coding RNAs that regulate gene expression by interfering with protein translational machinery and/or inducing degradation of target mRNAs [1]. Since the discovery of miRNAs, much effort has been made to understand the mechanisms by which miRNAs are synthesized and involved in cell lineage development and human diseases, especially, cancer. It is imperative that scientists continue to delineate how the biogenesis of these miRNAs is controlled by the cellular processing machinery, so that one may better understand how to modulate their expression or function as it contributes to a unique disease state. Recent research shows the involvement of additional proteins that modulate the function of the miRNA processing machinery, the Drosha processing complex, or microprocessor. This article reviews these new findings and discusses the potential for targeting these regulatory pathways in cancer therapy.It has been well-established that the biogenesis of microRNAs (miRNAs) involves three step-wise processes, including transcription of primary miRNAs (pri-miRNAs) from the miRNA genes [2], partially processed precursor miRNAs (pre-miRNAs) in nuclei [3] and the mature miRNAs that were generated in the cytoplasm (Fig. 1). Pri-miRNA is typically a large RNA polymerase pol II-derived transcript whose tertiary structure forms stem loop structures. The stem loop is cleaved off by the microprocessor machinery, Drosha complex, to form ~60-100 nucleotide long pre-miRNA, which is further processed into ~22 nucleotide long mature miRNAs by Dicer, a RNase III enzyme, following translocation from the nuclei to cytoplasm [4].After successful cleavage, the pre-miRNA is bound by exportin-5 in a ran-GTP dependant manner and exported from the nucleus [5-7]. Binding of pre-miRNA by exportin-5 is dependent upon the stem of the miRNA, requiring a length of 16-18 base pairs, and alterations in the 3' overhang will affect the efficiency of exp
Identification of MicroRNAs as Potential Prognostic Markers in Ependymoma  [PDF]
Fabricio F. Costa, Jared M. Bischof, Elio F. Vanin, Rishi R. Lulla, Min Wang, Simone T. Sredni, Veena Rajaram, Maria de Fátima Bonaldo, Deli Wang, Stewart Goldman, Tadanori Tomita, Marcelo B. Soares
PLOS ONE , 2011, DOI: 10.1371/journal.pone.0025114
Abstract: Introduction We have examined expression of microRNAs (miRNAs) in ependymomas to identify molecular markers of value for clinical management. miRNAs are non-coding RNAs that can block mRNA translation and affect mRNA stability. Changes in the expression of miRNAs have been correlated with many human cancers. Materials and Methods We have utilized TaqMan Low Density Arrays to evaluate the expression of 365 miRNAs in ependymomas and normal brain tissue. We first demonstrated the similarity of expression profiles of paired frozen tissue (FT) and paraffin-embedded specimens (FFPE). We compared the miRNA expression profiles of 34 FFPE ependymoma samples with 8 microdissected normal brain tissue specimens enriched for ependymal cells. miRNA expression profiles were then correlated with tumor location, histology and other clinicopathological features. Results We have identified miRNAs that are over-expressed in ependymomas, such as miR-135a and miR-17-5p, and down-regulated, such as miR-383 and miR-485-5p. We have also uncovered associations between expression of specific miRNAs which portend a worse prognosis. For example, we have identified a cluster of miRNAs on human chromosome 14q32 that is associated with time to relapse. We also found that miR-203 is an independent marker for relapse compared to the parameters that are currently used. Additionally, we have identified three miRNAs (let-7d, miR-596 and miR-367) that strongly correlate to overall survival. Conclusion We have identified miRNAs that are differentially expressed in ependymomas compared with normal ependymal tissue. We have also uncovered significant associations of miRNAs with clinical behavior. This is the first report of clinically relevant miRNAs in ependymomas.
A Potential of microRNAs for High-Content Screening  [PDF]
Andrius Serva,Christoph Claas,Vytaute Starkuviene
Journal of Nucleic Acids , 2011, DOI: 10.4061/2011/870903
Abstract: In the last years miRNAs have increasingly been recognised as potent posttranscriptional regulators of gene expression. Possibly, miRNAs exert their action on virtually any biological process by simultaneous regulation of numerous genes. The importance of miRNA-based regulation in health and disease has inspired research to investigate diverse aspects of miRNA origin, biogenesis, and function. Despite the recent rapid accumulation of experimental data, and the emergence of functional models, the complexity of miRNA-based regulation is still far from being well understood. In particular, we lack comprehensive knowledge as to which cellular processes are regulated by which miRNAs, and, furthermore, how temporal and spatial interactions of miRNAs to their targets occur. Results from large-scale functional analyses have immense potential to address these questions. In this review, we discuss the latest progress in application of high-content and high-throughput functional analysis for the systematic elucidation of the biological roles of miRNAs. 1. Introduction miRNAs (microRNAs) are 17-nt to 24-nt long noncoding RNAs that regulate gene expression in metazoans. miRNAs act by partially or completely complementary binding to their target mRNAs, resulting in translational repression and/or mRNA degradation [1, 2]. miRNAs are predicted to affect the expression of nearly 60% of protein-coding mammalian genes [3, 4] and, thereby, to control many, if not all, biological processes. Fundamental changes at the cellular and organismal level, including development [5], aging [6], the stress response [7], cell proliferation [8, 9], and apoptosis [10, 11], were shown to be regulated by miRNAs. Furthermore, miRNAs have been implicated in various diseases, such as diabetes [12–14], cancer [15, 16], hepatitis C [17], neurodevelopmental (reviewed in [18]), and mental [19] disorders. Rapidly growing knowledge of miRNAs as potent regulators in health and disease makes miRNAs attractive as targets for therapeutic intervention [20, 21] as well as for diagnostic markers [22, 23]. Numerous previous publications have addressed miRNA biogenesis and action (for detailed reviews see [24, 25]). Briefly, miRNAs are transcribed as long primary transcripts (pri-miRNAs), most of which are polyadenylated and capped. Pri-miRNAs are initially cleaved in nucleus by a multiprotein complex, called Microprocessor, yielding ~70-nt long stem-loop structured precursor miRNAs (pre-miRNAs). The key components of the Microprocessor complex are the RNase III enzyme Drosha and the double-stranded
Serum MicroRNAs Are Promising Novel Biomarkers  [PDF]
Shlomit Gilad, Eti Meiri, Yariv Yogev, Sima Benjamin, Danit Lebanony, Noga Yerushalmi, Hila Benjamin, Michal Kushnir, Hila Cholakh, Nir Melamed, Zvi Bentwich, Moshe Hod, Yaron Goren, Ayelet Chajut
PLOS ONE , 2008, DOI: 10.1371/journal.pone.0003148
Abstract: Background Circulating nucleic acids (CNAs) offer unique opportunities for early diagnosis of clinical conditions. Here we show that microRNAs, a family of small non-coding regulatory RNAs involved in human development and pathology, are present in bodily fluids and represent new effective biomarkers. Methods and Results After developing protocols for extracting and quantifying microRNAs in serum and other body fluids, the serum microRNA profiles of several healthy individuals were determined and found to be similar, validating the robustness of our methods. To address the possibility that the abundance of specific microRNAs might change during physiological or pathological conditions, serum microRNA levels in pregnant and non pregnant women were compared. In sera from pregnant women, microRNAs associated with human placenta were significantly elevated and their levels correlated with pregnancy stage. Conclusions and Significance Considering the central role of microRNAs in development and disease, our results highlight the medically relevant potential of determining microRNA levels in serum and other body fluids. Thus, microRNAs are a new class of CNAs that promise to serve as useful clinical biomarkers.
Signature of Circulating MicroRNAs as Potential Biomarkers in Vulnerable Coronary Artery Disease  [PDF]
Jingyi Ren, Jing Zhang, Ning Xu, Guanping Han, Qiang Geng, Junxian Song, Sufang Li, Jianqing Zhao, Hong Chen
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0080738
Abstract: Aims MicroRNAs (miRNAs) play important roles in the pathogenesis of cardiovascular diseases. Circulating miRNAs were recently identified as biomarkers for various physiological and pathological conditions. In this study, we aimed to identify the circulating miRNA fingerprint of vulnerable coronary artery disease (CAD) and explore its potential as a novel biomarker for this disease. Methods and Results The Taqman low-density miRNA array and coexpression network analyses were used to identify distinct miRNA expression profiles in the plasma of patients with typical unstable angina (UA) and angiographically documented CAD (UA group, n = 13) compared to individuals with non-cardiac chest pain (control group, n = 13). Significantly elevated expression levels of miR-106b/25 cluster, miR-17/92a cluster, miR-21/590-5p family, miR-126*, and miR-451 were observed in UA patients compared to controls. These findings were validated by real-time PCR in another 45 UA patients, 31 stable angina patients, and 37 controls. In addition, miR-106b, miR-25, miR-92a, miR-21, miR-590-5p, miR-126* and miR-451 were upregulated in microparticles (MPs) isolated from the plasma of UA patients (n = 5) compared to controls (n = 5). Using flow cytometry and immunolabeling, we further found that Annexin V+ MPs were increased in the plasma samples of UA patients compared to controls, and the majority of the increased MPs in plasma were shown to be Annexin V+ CD31+ MPs. The findings suggest that Annexin V+ CD31+ MPs may contribute to the elevated expression of the selected miRNAs in the circulation of patients with vulnerable CAD. Conclusion The circulating miRNA signature, consisting of the miR-106b/25 cluster, miR-17/92a cluster, miR-21/590-5p family, miR-126* and miR-451, may be used as a novel biomarker for vulnerable CAD. Trial Registration Chinese Clinical Trial Register, ChiCTR-OCH-12002349.
Page 1 /100
Display every page Item


Home
Copyright © 2008-2017 Open Access Library. All rights reserved.