MicroRNAs—缺血性脑卒中潜在的诊断标志物及治疗靶点

摘要: 缺血性脑卒中由局部脑组织血液供应障碍所致,具有发病率、致残率和致死率高的特征。由于其形成机制复杂及现有的预防与治疗手段有限,缺血性脑卒中已成为严重影响人类健康的重要疾病。MicroRNAs（miRNAs）是一类内源性、非编码小核糖核酸分子,进化上高度保守。在细胞增殖、凋亡、分化等过程中发挥重要作用。近年来研究发现,在脑缺血的条件下,miRNAs表达谱发生异常改变,多种miRNAs参与调节脑缺血后的病理过程,是缺血性脑卒中潜在的诊断、病情监测新型标志物及治疗靶点。     

miRNAs表达谱在肺肿瘤中的临床应用

正miRNAs是一类长约22个核苷酸的内源性非编码、单链小分子RNA,主要通过与靶mRNA的3′-UTR互补结合,导致靶mRNA降解或抑制翻译,在转录后水平上调控靶基因表达[1]。近年来有关miRNAs与肺癌的报道越来越多,并成为当前研究的一个热点。大量的研究表明miRNAs在人类肿瘤的发生发展中发挥了重要的作用,作为潜在的生物标志物,具     

食管鳞癌相关microRNAs研究进展

食管癌是癌症患者的常见死因,其中食管鳞癌是主要类型。微小RNA(microRNAs,miRNAs)是一种非编码的内源性RNA分子。随着检测技术的发展,使miRNA有望成为诊断和治疗食管鳞癌的新的分子生物学标志物。循环miRNAs测定有望成为简便的监测食管鳞癌发生、发展的方法。本文对食管鳞癌相关miRNAs的表达、功能、作用机制及其临床应用前景等方面作一综述。     

MicroRNAs与肾相关疾病诊断的研究进展

肾脏代偿功能强大,肾相关疾病早期症状不明显,易延误治疗契机导致肾脏不可逆性病变,严重影响人类生存和生活质量。微小RNAs(microRNAs,miRNAs)在机体的生长发育中必不可少,研究表明,miRNAs在疾病的发生、发展以及预后中发挥着重要作用。本文就近年来miRNAs在肾相关疾病早期诊断和预后评价中的研究进展作一综述。     

MicroRNA调控肿瘤干细胞凋亡的研究进展

摘要： 微小核糖核酸（microRNAs,miRNAs)是一类内源性非蛋白质编码小RNAs,主要在转录后水平负性调控基因表达。miRNAs表达水平的改变与许多人类疾病尤其是癌症密切相关。肿瘤干细胞(CSCs)亦称为肿瘤起源细胞,是存在于肿瘤细胞中的一小群具有干细胞特性的亚群细胞,具有高度致瘤性及耐药性。近年来,miRNAs在CSCs凋亡调控中的作用逐渐成为研究热点。靶向miRNAs的分子疗法有望成为校正CSCs调节异常的有力工具。了解CSCs凋亡信号系统的分子机制对开发新型癌症疗法尤为重要。本文就miRNAs与CSCs凋亡相关研究作一综述。     

微小核糖核酸在乳腺癌中的研究进展

微小核糖核酸(miRNAs)是一类具有调控功能的小分子非编码核糖核酸,与人类众多疾病的发生有关。miRNAs稳定性好,可反复取样检测,被认为是最具潜力的肿瘤标志物之一。研究证实了miRNAs对乳腺癌发生发展、侵袭转移、诊断治疗及预后检测的作用。本文就近年来该方面的研究进展进行综述。     

microRNAs在肿瘤病理学研究中的进展

microRNAs （miRNAs）是一类长度约为20～23 nt的内源性小分子单链非编码RNA,其位于基因组内非编码区,进化上高度保守,可在转录后水平对基因表达进行调节.miRNAs通过调控基因表达、在细胞增殖、凋亡、分化及个体发育等过程中发挥着非常重要的作用.近十多年的研究[4,5]已证实,miRNAs与肿瘤的发生及发展关系密切,通过调控其靶基因的表达从而影响肿瘤的发生发展,发挥着类似癌基因或抑癌基因的作用.这些与肿瘤相关的miRNAs对肿瘤的诊断、治疗及判断预后都具有重要的意义及应用前景.     

循环MicroRNAs在常见肿瘤诊疗中研究进展

恶性肿瘤是当今世界严重危害人类健康的重大疾病之一,早期诊断、早期治疗是肿瘤防治的基本策略。MicroRNAs(miRNAs)是一类非编码小RNA,在许多肿瘤发生发展中起重要作用,且循环miRNAs比较稳定、易获取,被认为是非常有前景的肿瘤生物学标志物,目前已有应用循环miRNAs诊断肿瘤的较多探索。本文就循环MicroRNAs在肿瘤诊断研究中的进展作一综述。     

糖尿病及其并发症中microRNAs的作用

糖尿病及其并发症严重威胁着人类健康，它们的发生可能涉及到多重复杂因素，然而，具体的发病机制尚不明确。MicroRNAs（miRNAs）是一系列全新的非编码小分子RNAs，其参与人体许多生理和病理过程的调控。新近研究发现，miRNAs在糖尿病及其相关并发症的发病机制中起着重要作用，这些相关miRNAs也为糖尿病的诊断和治疗提供了一个全新视角。     

miRNAs在心血管疾病中的研究进展

微小RNAs(miRNAs)是一种内源性短链RNA,长度约22 nt,具有高度保守性,不具备编码作用。成熟的miRNAs通过与目标基因3′端非翻译区特异性结合发挥作用,在转录后水平降解该基因的mRNAs或阻碍其翻译,从而负性调控目标基因表达而发挥生物学功能。近年来,miRNAs在心血管疾病中的研究日益深入,大量证据显示,miRNAs在许多心血管疾病发病机制中发挥作用,也将成为潜在的心血管疾病诊断与预后评价的标志物和新的治疗靶点。     

Evaluating the consistency of differential expression of microRNA detected in human cancers

Differential expression of microRNA (miRNA) is involved in many human diseases and could potentially be used as a biomarker for disease diagnosis, prognosis, and therapy. However, inconsistency has often been found among differentially expressed miRNAs identified in various studies when using miRNA arrays for a particular disease such as a cancer. Before broadly applying miRNA arrays in a clinical setting, it is critical to evaluate inconsistent discoveries in a rational way. Thus, using data sets from 2 types of cancers, our study shows that the differentially expressed miRNAs detected from multiple experiments for each cancer exhibit stable regulation direction. This result also indicates that miRNA arrays could be used to reliably capture the signals of the regulation direction of differentially expressed miRNAs in cancer. We then assumed that 2 differentially expressed miRNAs with the same regulation direction in a particular cancer play similar functional roles if they regulate the same set of cancer-associated genes. On the basis of this hypothesis, we proposed a score to assess the functional consistency between differentially expressed miRNAs separately extracted from multiple studies for a particular cancer. We showed although lists of differentially expressed miRNAs identified from different studies for each cancer were highly variable, they were rather consistent at the level of function. Thus, the detection of differentially expressed miRNAs in various experiments for a certain disease tends to be functionally reproducible and capture functionally related differential expression of miRNAs in the disease.     

The potential of miRNAs for diagnosis,treatment and monitoring of breast cancer

Abstract

Dysregulation of microRNAs (miRNAs) has a fundamental role in the initiation, development and progression of several human cancers, including breast cancer (BC), since strong evidence has shown that miRNAs can regulate the expression of oncogenes or tumor suppressor genes. A possible role of miRNAs in the diagnosis in BC has been demonstrated. As miRNAs has been found stable in biofluids, extracellular multiple miRNA profiles have been proposed as diagnostic tools, showing better diagnostic performance than individual miRNAs in BC. In this paper, based on the current literature, we present the role of microRNAs in the diagnosis and therapy monitoring of BC. Furthermore, we report new miRNA-based drugs that could be turned into promising therapy for BC, alone or in combination with conventional therapy. We also discuss how extracellular miRNAs could become new, easily accessible, affordable, non-invasive tools for BC patients.     

Roles of microRNAs and their targets in cancer

MicroRNAs (miRNAs) are a new class of regulator of gene expression. Initially discovered as regulators of developmental timing in invertebrates, miRNAs have subsequently been implicated in a variety of biologic processes. In recent years, their importance for human disease has become apparent. In particular, there is increasing evidence of their role in cancer, both as oncogenes and tumor suppressors, making them appealing targets for therapy. Furthermore, the variations in the abundance of miRNAs in different tissues and cancers offer a specific 'signature' that can be useful in diagnosis.     

Roles of microRNAs and their targets in cancer

MicroRNAs (miRNAs) are a new class of regulator of gene expression. Initially discovered as regulators of developmental timing in invertebrates, miRNAs have subsequently been implicated in a variety of biologic processes. In recent years, their importance for human disease has become apparent. In particular, there is increasing evidence of their role in cancer, both as oncogenes and tumor suppressors, making them appealing targets for therapy. Furthermore, the variations in the abundance of miRNAs in different tissues and cancers offer a specific ‘signature’ that can be useful in diagnosis.     

MicroRNAs as potential target gene in cancer gene therapy of gastrointestinal tumors

INTRODUCTION: MicroRNA (miRNA) is a small non-coding RNA, which negatively regulates the expression of many target genes, thereby contributing to the modulation of diverse cell fates. Recent advances in molecular biology have revealed the potential role of miRNAs in tumor initiation, progression and metastasis. Aberrant regulation of miRNAs has been frequently reported in a variety of cancers, including gastrointestinal tumors, suggesting that cancer-related miRNAs are promising as novel biomarkers for tumor diagnosis and are potential target genes for cancer gene therapy against gastrointestinal tumors. AREAS COVERED: The review focuses on the role of specific miRNAs (miR-192/194/215 and miR-7) in the differentiation of gastrointestinal epithelium and on the role of tumor-suppressive (miR-34, miR-143, miR-145) and oncogenic miRNAs (miR-21, miR-17-92 cluster) in gastrointestinal tumors. Furthermore, the potential role of miRNAs as novel biomarkers and target genes for cancer gene therapy against gastrointestinal tumors are discussed. We will also outline the potential clinical application of miRNAs for tumor diagnosis and cancer gene therapy against gastrointestinal tumors. EXPERT OPINION: Exploration of tumor-related miRNAs would provide important opportunities for the development of novel cancer gene therapies aimed at normalizing the critical miRNAs that are deregulated in gastrointestinal tumors.     

Circulating microRNAs: a novel class of biomarkers to diagnose and monitor human cancers

Specific and sensitive non-invasive biomarkers for the detection of human epithelial malignancies are urgently required to reduce the worldwide morbidity and mortality caused by cancer. MicroRNAs (miRNAs) are 19-24 nt noncoding RNAs that are frequently dysregulated in cancer and have shown great promise as tissue-based markers for cancer classification. Once thought to be unstable RNA molecules, miRNAs are now shown to be stably expressed in serum, plasma, urine, saliva, and other body fluids. Moreover, the unique expression patterns of these circulating miRNAs are correlated with certain human diseases, including various types of cancer. Therefore, tumor-derived miRNAs in serum or plasma are emerging as novel blood-based fingerprints for the detection of human cancers, especially at an early stage. This review presented newly uncovered cellular and molecular mechanisms of the sources and stability of circulating miRNAs, revealing their great potential as a class of highly specific and sensitive biomarkers for tumor classification and prognostication. Meanwhile, this review also addressed certain critical issues that hinder the wide application of this new approach. Some potential challenges for the transition of circulating miRNAs from a research setting to a clinical application were also highlighted, with a future perspective of the incorporation of circulating miRNAs in the field of clinical oncology, especially their great potential from diagnostic to prognostic and predictive applications.     

The malignant phenotype-associated microRNA in gastroenteric,hepatobiliary and pancreatic carcinomas

Importance of the field: MicroRNA (miRNA) is a newly discovered class of small and endogenous non-coding RNAs. Many miRNAs exhibit altered expression levels in cancer, and they can affect the cancerous phenotype of malignant cells.

Areas covered in this review: We review the recent advances in miRNA involvement in human gastroenteric tumor and analyze the clinical and therapeutic opportunities they provide. We envisage future developments toward molecular mechanisms of miRNAs and their potential applications to cancer treatment.

What the reader will gain: MiRNAs may reasonably become novel anticancer tools. More investigations should be performed to promote the success of therapeutic–clinical use of miRNAs in cancer.

Take home message: Future studies should focus on identification of new miRNAs and targets, the function and mechanism of miRNA-regulated cancer pathogenesis, the reliable delivery strategy and the novel type of miRNA-based therapy.     

The role of small RNAs in human diseases: potential troublemaker and therapeutic tools

Small RNAs, including short interfering RNAs (siRNAs) and microRNAs (miRNAs), are ubiquitous, versatile repressors of gene expression in plants, animals, and many fungi. They can trigger destruction of homologous mRNA or inhibition of cognate mRNA translation and play an important role in maintaining the stable state of chromosome structure and regulating the expression of protein-coding genes. Furthermore, the recent research showed that there exists close relationship between small RNAs and human diseases. Several human diseases have surfaced in which miRNAs or their machinery might be implicated, such as some neurological diseases and cancers. The specificity and potency of small RNAs suggest that they might be promising as therapeutic agents. This article will review the role of small RNAs in some human diseases etiology and investigations of taking siRNAs as therapeutic tools for treating viral infection, cancer, and other diseases. We also discuss the potential of miRNAs in gene therapy.     

MicroRNAs as potential target gene in cancer gene therapy of gastrointestinal tumors

Introduction: MicroRNA (miRNA) is a small non-coding RNA, which negatively regulates the expression of many target genes, thereby contributing to the modulation of diverse cell fates. Recent advances in molecular biology have revealed the potential role of miRNAs in tumor initiation, progression and metastasis. Aberrant regulation of miRNAs has been frequently reported in a variety of cancers, including gastrointestinal tumors, suggesting that cancer-related miRNAs are promising as novel biomarkers for tumor diagnosis and are potential target genes for cancer gene therapy against gastrointestinal tumors.

Areas covered: The review focuses on the role of specific miRNAs (miR-192/194/215 and miR-7) in the differentiation of gastrointestinal epithelium and on the role of tumor-suppressive (miR-34, miR-143, miR-145) and oncogenic miRNAs (miR-21, miR-17-92 cluster) in gastrointestinal tumors. Furthermore, the potential role of miRNAs as novel biomarkers and target genes for cancer gene therapy against gastrointestinal tumors are discussed. We will also outline the potential clinical application of miRNAs for tumor diagnosis and cancer gene therapy against gastrointestinal tumors.

Expert opinion: Exploration of tumor-related miRNAs would provide important opportunities for the development of novel cancer gene therapies aimed at normalizing the critical miRNAs that are deregulated in gastrointestinal tumors.