miRNA对水稻生长发育的调控

MicroRNA(miRNA)是一类小的非编码RNA,它们主要在转录后水平对靶mRNA进行切割或抑制mRNA的翻译来调控基因的表达. miRNA通过对靶基因的调控参与植物的生长发育、胁迫应答和代谢过程.在水稻中,已经发现并初步验证了许多与生长发育相关的miRNA,它们对水稻不同器官和形态发育发挥着重要作用.本文综述了水稻miRNA的发生和调控机制、靶基因的预测,重点介绍了miRNA对水稻生长发育和形态建成的研究进展,并对研究过程中存在的问题进行了讨论.为更好地了解miRNA及其靶基因在提高水稻产量和品质方面的作用,进一步解析miRNA在水稻中的调控机制提供参考.     

微RNA与肺癌

微RNA(microRNA,miRNA)是一类长度为21～22nt的非编码RNA分子,其通过转录后基因沉默调控靶基因的活性,在包括肺癌在内的肿瘤发生中起重要作用。随着对miRNA靶基因及miRNA分子行为认识的提高,miRNA很有可能成为癌症治疗新的途径。本文介绍了miRNA的生成,miRNA在肺癌中的作用机理及诊断治疗方面的最新进展。     

Argonaute蛋白质在miRNA基因调控中的作用

miRNA(microRNA)是一类长约22 nt,具有调控功能的内源性非编码小RNA。成熟miRNA由RNA聚合酶II/III转录的初级转录物经过一系列酶剪切加工产生,最终与Argonaute蛋白质等复合为沉默效应复合物(RNA-induced silencing complex,RISC)。miRNA通过与靶基因完全或部分序列互补配对,指导RISC对靶基因进行降解或翻译抑制。Argonaute作为RISC的主要效应蛋白,在miRNA的生成及靶基因的调控过程中起着重要作用。该文综述了Argonaute在miRNA介导的基因调控中的作用,以期有助于miRNA调控网络的研究及机制的阐释。     

环状RNA:潜在的新型miRNA活性调控分子

环状RNA(circular RNA,circRNA)是近年来RNA领域最新的研究热点.它是一类由特殊的选择性剪切产生且在真核细胞中广泛表达的环形内源性RNA分子.研究发现,circRNA富含microRNA(miRNA)结合位点,可以发挥竞争性内源RNA作用,作为miRNA"海绵"来解除对其靶基因的抑制效应.近年来,circRNA作为一种新型调控分子调控miRNA功能的发挥,受到众多研究者的青睐.本文综述circRNA的产生机制,及其调控miRNA的最新研究进展与研究方法等.     

植物MicroRNA的特点与研究方法

MicroRNAs(miRNAs)是一类在植物、动物、单细胞藻类和病毒等中存在的具有调控基因表达作用的内源非编码小RNA(small RNAs).在植物中,miRNAs主要依靠与靶基因之间完全或近乎完全的互补配对切割靶基因或翻译抑制实现其调控功能.主要综述植物miRNA的特点,并介绍miRNA的获得方式、靶基因预测及验证方法.     

微小RNA在心肌重塑中的作用

微小RNA (microRNA, miRNA)是一类含有约22个核苷酸的内源性非编码RNA, 通过与靶mRNA的3′非翻译区(3′ UTR)互补配对, 抑制翻译或促进靶mRNA的降解介导转录后基因调控,涉及多种生物学过程.目前研究表明,miRNA参与了心脏的发育、病理性心肌肥大等过程,表明miRNA可作为新的治疗心肌肥大的靶向分子.本文就新近有关miRNA在心肌重塑中的研究进展予以综述.     

青花菜细胞质雄性不育相关miRNA的鉴定与表达特征分析

植物miRNA是一类内源小分子RNA,在花粉发育和育性调控中具有重要作用.该研究利用高通量测序技术构建了青花菜细胞质雄性不育系及其保持系花蕾的sRNA文库,并通过qRT-PCR技术检测育性相关的miRNAs及其预测靶基因的表达特征,为深入探讨miRNA调控青花菜育性机制提供理论依据.结果表明:(1)在青花菜中共鉴定到1...     

microRNA参与植物次生代谢与非生物胁迫的调控

微RNA(microRNA,miRNA)为广泛存在于真核生物中的约16 ～ 29个核苷酸长度的内源非编码单链RNA分子,在植物中参与细胞增殖、分化、代谢、器官形成以及抵御盐、温度、干旱、重金属胁迫等方面的调节.植物miRNA主要通过对靶基因降解或抑制靶基因的表达,影响植物的生长发育.目前对miRNA的产生与调控方式的研...     

MicroRNAs在肿瘤中对mTOR通路的影响

MicroRNAs(miRNA)是一类长度为18~23 nt的非编码单链RNA,通过与靶mRNA的非编码区特异性结合,在转录后水平调控基因的表达。哺乳动物雷帕霉素靶蛋白(mTOR)与肿瘤的进程密切相关。现综述了与mTOR信号通路相关的miRNA及其在肿瘤中研究的最新进展,并探讨miRNA及其靶基因在肿瘤诊断和治疗中的应用。     

miRNA 的生物合成过程

MicroRNA (miRNA) 是一类真核生物内源性的小分子单链 RNA ,通常为 18 ～ 25 nt 长,能够通过与靶 mRNA 特异性的碱基配对引起靶 mRNA 的降解或者抑制其翻译,从而对基因进行转录后的表达调控 . 近几年来,在动物细胞和植物组织中,上百种 miRNA 被陆续发现 . 这些小分子调控 RNA 是从 60 ～ 200 nt 的具有发夹状结构的前体中被切割出来而成熟的,在动物细胞中, miRNA 基因的转录初产物 (pri-miRMA) 很快被一种核糖核酸酶Ⅲ Drosha 加工成为 miRNA 前体 (pre-miRNA) ,然后由细胞核转运至细胞质中,经另一种核糖核酸酶Ⅲ Dicer 识别剪切为成熟 miRNA. 对这一过程进行了简要的综述,并且对植物 miRNA 的成熟过程也进行了探讨 . 对 miRNA 的生物合成过程的深入了解,将有助于研究这一类起重要调控作用的 RNA 是如何行使功能的,从而进一步研究其在生长发育及各种疾病中所起的重要作用 .     

New insight into the role of miRNAs in leukemia

Recent studies have shown that microRNAs(miRNAs) play an important role in cell differentiation, growth, and death, including the functional study of miRNAs in tumorigenesis. To date, miRNA expression profiles in many types of cancers have been identified and miRNA expression signatures associated with types and cytogenetics of leukemia have also been reported. Increasing evidence has shown that miRNAs could function as either tumor suppressors or oncogenes in cancers such as leukemia, while other miRNAs might be benefitcial for diagnosis and prognosis, predicted to be newly developed biomarkers. In this review, we summarize the recent progress about miRNAs in leukemia and present a miRNA-mediated network involved in differentiation, proliferation and apoptosis predicted to be the roles of miRNAs in the pathogenesis of leukemia. Supported by National Natural Science Foundation of China (Grant No. 30672254 and 30872784), National High-Tech Research and Development Program of China (Grant No. 2008AA02Z106).     

Characterization of miRNomes in Acute and Chronic Myeloid Leukemia Cell Lines

Myeloid leukemias are highly diverse diseases and have been shown to be associated with microRNA（miRNA） expression aberrations. The present study involved an in-depth miRNome analysis of two human acute myeloid leukemia（AML） cell lines, HL-60 and THP-1, and one human chronic myeloid leukemia（CML） cell line, K562, via massively parallel signature sequencing. mRNA expression profiles of these cell lines that were established previously in our lab facilitated an integrative analysis of miRNA and mRNA expression patterns. miRNA expression profiling followed by differential expression analysis and target prediction suggested numerous miRNA signatures in AML and CML cell lines. Some miRNAs may act as either tumor suppressors or oncomiRs in AML and CML by targeting key genes in AML and CML pathways. Expression patterns of cell type-specific miRNAs could partially reflect the characteristics of K562, HL-60 and THP-1 cell lines, such as actin filament-based processes, responsiveness to stimulus and phagocytic activity. miRNAs may also regulate myeloid differentiation, since they usually suppress differentiation regulators. Our study provides a resource to further investigate the employment of miRNAs in human leukemia subtyping, leukemogenesis and myeloid development. In addition, the distinctive miRNA signatures may be potential candidates for the clinical diagnosis, prognosis and treatment of myeloid leukemias.     

miR-345-5p regulates proliferation,cell cycle,and apoptosis of acute myeloid leukemia cells by targeting AKT2

Acute myeloid leukemia (AML) is a malignant clonal hematopoietic disease, which is caused by hematopoietic stem cell abnormalities. Epigenetic regulation, especially of microRNAs (miRNAs), mostly results from external or environmental effects and is critical to AML. In this study, for the first time, we report that decreased expression of miR-345-5p facilitates the proliferation of leukemia cells in AML. Further study demonstrated that AKT1/2 was the target of miR-345-5p and was responsible for the dysregulation of leukemia cell proliferation and apoptosis. Inhibition of AKT1/2 ameliorated this malignant effect, which provides new insight into AML diagnosis, treatment, prognosis, and next-step translational investigations.     

Identification of Circulating MicroRNAs as Potential Biomarkers for Detecting Acute Myeloid Leukemia

Acute myeloid leukemia (AML) is the most common acute leukemia in adults. The disease is characterized by various cytogenetic and molecular abnormalities with distinct prognoses and gene expression profiles. Emerging evidence has suggested that circulating microRNAs (miRNAs) could serve as noninvasive biomarkers for cancer detection; however, little is known about circulating miRNA profiles in AML patients. In this study, a genome-wide serum miRNA expression analysis was performed using Solexa sequencing for initial screen, followed by validation with real-time PCR assays. The analysis was conducted on training and verification sets of serum samples from 140 newly diagnosed AML patients and 135 normal adult donors. After a two-phase selection and validation process, 6 miRNAs, miR-10a-5p, miR-93-5p, miR-129-5p, miR-155-5p, miR-181b-5p and miR-320d, were found to have significantly different expression levels in AML compared with control serum samples. Furthermore, unsupervised clustering analysis revealed the remarkable ability of the 6-miRNA profile to differentiate between AML patients and normal controls. The areas under the ROC curve for the selected miRNAs ranged from 0.8129 to 0.9531. More importantly, miR-181b-5p levels in serum were significantly associated with overall survival. These data demonstrated that the expression patterns of circulating miRNAs were systematically altered in AML and miR-181b-5p may serve as a predictor for overall survival in AML patients.     

Effective and specific control of aml1/eto gene expression in acute myeloid leukemia cells by lentivecior-based RNA-interference

In presented work, new approach for the control of aml1/eto gene expression in t(8;21)(q22;q22)-positive acute myeloid leukemia cells has been developed. The technique is based on using the RNA-interference and lentiviral transduction methodology. Two new lentiviral vector sets for induction of constitutive anti-aml1/eto RNA-interference in acute myeloid leukemia cells have been developed and tested. The first set was based on use of artificial microRNAs (miRNAs) and second one was intended for production of short hairpin RNAs (shRNAs). It was shown that Kasumi-1 and SKNO-1 leukemia cells can be efficiency transduced by each new lentiviral vector. Moreover, the percent of modified leukemia cells that may be easily evaluated in multiplicity of infection (MOI) test achieved more than 90% for Kasumi-1 and SKNO-1 cells at MOI 40 and 20, respectively. Comparative study elucidated that the anti-aml1/eto shRNA-based approach induced a stronger knock-down of aml1/eto gene in Kasumi-1 and SKNO-1 cells than the miRNA-based method did. We hope that the proposed approach may become useful instrument for controlling the aml1/eto gene expression in vitro as well as in vivo investigations of function and biological role of the gene.     

miR-29a and miR-142-3p downregulation and diagnostic implication in human acute myeloid leukemia

Expression profiling of microRNAs (miRNAs) in most diseases might be popular and provide the possibility for diagnostic implication, but few studies have accurately quantified the expression level of dysregulated miRNAs in acute myeloid leukemia (AML). In this study, we analyzed the peripheral blood mononuclear cells (PBMCs) from 10 AML patients (subtypes M1 to M5) and six normal controls by miRNA microarray and identified several differentially expressed miRNAs. Among them miR-29a and miR-142-3p were selectively encountered in Northern blot analysis and their significantly decreased expression in AML was further confirmed. Quantitative real-time PCR in 52 primarily diagnosed AML patients and 100 normal controls not only verified the expression properties of these 2 miRNAs, but also established that the expression level of miR-142-3p and miR-29a in PBMCs could be used as novel diagnostic markers. A better diagnostic outcome was achieved by combining miR-29a and miR-142-3p with about 90% sensitivity, 100% specificity, and an area under the ROC curve (AUC) of 0.97. Our results provide insights into the involvement of miRNAs in leukemogenesis, and offer candidates for AML diagnosis and therapeutic strategy.     

Alterations in The Plasma Expression of mir-15b,mir-195 and the Tumor-Suppressor Gene DLEU7 in Patients with B-Cell Chronic Lymphocytic Leukemia

Background:Chronic lymphocytic leukemia (CLL) is one of the most prevalent forms of leukemia in adults. Inactivation of the DLEU7 gene is frequently observed in patients with CLL. Furthermore, microRNAs (miRNAs) have been observed to have a critical role in the pathogenesis of several cancers, including leukemia. Considering the tumor-suppressive role of DLEU7, as well as the tumor suppressor or oncogenic role of microRNAs (miRNAs), the aim of the present study was to evaluate the potential miRNAs targeting the DLEU7 gene in B-cells and explore expression changes these genes in the plasma of B-CLL patients. Methods:The miRNAs interacting with the DLEU7 gene were predicted and selected using bioinformatics tools. A total of 80 plasma samples were collected from 40 patients with B-cells and 40 healthy individuals, then subjected to RNA extraction and cDNA synthesis. The expression profiles of the predicted miRNAs and the DLEU7 gene in the plasma of B-CLL patients and healthy individuals were determined by RT-qPCR analysis. Results:The bioinformatics prediction indicated that miR-15b and miR-195 target the DLEU7 gene. The expression levels of miR-15b and miR-195 were significantly higher in the plasma of patients with B-CLL compared to the healthy individuals (91.6, p= 0.001) (169, p= 0.001). However, the expression level of the DLEU7 gene was found to be significantly lower in the patient group compared to healthy controls (0.304, p= 0.001).Conclusion:Both miR-15b and miR-195, have the potential to function as novel and non-invasive biomarkers in the diagnosis and prognosis of patients with B-CLL.Key Words: B-CLL, miRNA, Biomarker, DLEU7, RT-QPCR     

Expression signatures of intragenic miRNAs and their corresponding host genes in myeloid leukemia cells

MicroRNAs (miRNAs) are a class of small non-coding RNAs involved in gene regulation. Approximately half of miRNAs are located within known genes and called intragenic miRNAs. 408 human intragenic miRNAs and their corresponding host genes were analyzed for genomic organization and functional characterization. Using quantitative real-time PCR, the expression levels of a subset of intragenic miRNAs and their host genes were examined in diverse myeloid leukemia cell lines, and their regulation in response to pharmacological stimuli was also evaluated. Expression of miR-22 strongly correlated with both myeloid leukemia subtypes and the expression of its host gene C17orf91 (p?<?0.05). The latter was absent in hematopoietic progenitors but abundant in erythroid and monocytic lineages. These results demonstrated that the expression signatures of miR-22 and C17orf91 are associated with developmental lineages and specific leukemia subtypes.