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microRNAs(miRNAs)是一类长约21~24个核苷酸的小分子非编码RNA,通过与位于靶基因mRNA 3' UTR区域的特异性结合位点互补配对结合,促进靶基因mRNA的降解和/或抑制翻译过程,从而行使调节基因表达的功能。miRNAs广泛存在于真核细胞内,参与了细胞的分化、增殖、凋亡、周期调控、迁移以及肿瘤的发生发展等多种生物学进程。miRNAs表达谱是一类潜在的强有力的评估肿瘤发生、发展、诊断、治疗及预后的生物学指标,在人类肿瘤的不同类型中均存在显著差异。乳腺癌是女性最常见的恶性肿瘤之一,不同类型的乳腺癌组织中miRNAs的表达谱也不同。本文对目前为止发现的一些与乳腺癌发生发展、转移及治疗反应等相关的miRNAs及其下游靶基因在乳腺癌中的表达及作用进行综述。   相似文献   

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microRNA(miRNA)是一类小RNA分子,在转录后水平对基因的表达进行调控。大量的证据显示绝大多数人类恶性肿瘤具有miRNA异常表型。miRNA与肿瘤中许多细胞过程如分化、增生和凋亡的改变有关。本文回顾了miRNA在肿瘤发生发展中的作用及其作为诊断、预后和治疗工具的可能性。   相似文献   

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 【摘要】 微小RNA (miRNA)是近年来在真核生物中发现的、在转录后水平负调控基因表达的一类长约22个核苷酸的非编码小分子RNA。miRNA生物学效应广泛,与细胞生长、凋亡、新陈代谢和信号转导等密切相关。已报道miRNA在各种肿瘤中表达失常,可能发挥着癌基因和抑癌基因的双重作用,同时越来越多的研究表明miRNA在调节肿瘤细胞对抗肿瘤药物耐药方面发挥着重要作用。系统深入地研究miRNA在肿瘤耐药中的机制,将为发展基于miRNA逆转肿瘤耐药的治疗策略提供重要的依据。  相似文献   

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微小RNA(miRNA)是近年来在真核生物中发现的、在转录后水平负调控基因表达的一类长约22个核苷酸的非编码小分子RNA.miRNA生物学效应广泛,与细胞生长、凋亡、新陈代谢和信号转导等密切相关.已报道miRNA在各种肿瘤中表达失常,可能发挥着癌基因和抑癌基因的双重作用,同时越来越多的研究表明miRNA在调节肿瘤细胞对抗肿瘤药物耐药方面发挥着重要作用.系统深入地研究miRNA在肿瘤耐药中的机制,将为发展基于miRNA逆转肿瘤耐药的治疗策略提供重要的依据.  相似文献   

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微小RNA(miRNA)是近年来在真核生物中发现的、在转录后水平负调控基因表达的一类长约22个核苷酸的非编码小分子RNA.miRNA生物学效应广泛,与细胞生长、凋亡、新陈代谢和信号转导等密切相关.已报道miRNA在各种肿瘤中表达失常,可能发挥着癌基因和抑癌基因的双重作用,同时越来越多的研究表明miRNA在调节肿瘤细胞对抗肿瘤药物耐药方面发挥着重要作用.系统深入地研究miRNA在肿瘤耐药中的机制,将为发展基于miRNA逆转肿瘤耐药的治疗策略提供重要的依据.  相似文献   

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微RNA(miRNA)在转录后水平调控靶基因的表达.头颈肿瘤中存在多种miRNA的差异表达,其参与细胞发育、增殖、分化、凋亡等一系列重要生物学进程,有望成为诊断治疗头颈肿瘤的有效手段.  相似文献   

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Jovanovic M  Hengartner MO 《Oncogene》2006,25(46):6176-6187
MicroRNAs (miRNAs) are small non-coding RNAs of about 18-24 nucleotides in length that negatively regulate gene expression. Discovered only recently, it has become clear that they are involved in many biological processes such as developmental timing, differentiation and cell death. Data that connect miRNAs to various kinds of diseases, particularly cancer, are accumulating. miRNAs can influence cancer development in many ways, including the regulation of cell proliferation, cell transformation, and cell death. In this review, we focus on miRNAs that have been shown to play a role in the regulation of apoptosis. We first describe in detail how Drosophila has been utilized as a model organism to connect several miRNAs with the cell death machinery. We discuss the genetic approaches that led to the identification of those miRNAs and subsequent work that helped to establish their function. In the second part of the review article, we focus on the involvement of miRNAs in apoptosis regulation in mammals. Intriguingly, many of the miRNAs that regulate apoptosis have been shown to affect cancer development. In the end, we discuss a virally encoded miRNA that influences the cell death response in the mammalian host cell. In summary, the data gathered over the recent years clearly show the potential and important role of miRNAs to regulate apoptosis at various levels and in several organisms.  相似文献   

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Breast cancer (BC) comprises a group of different diseases characterized by changes in tissue structure and gene expression. Recent advances in molecular biology have shed new light on the participation of genes and their products in the biology of BC. MicroRNAs (miRNAs) are small noncoding endogenous RNA molecules that appear to modulate the expression of more than a third of human genes, and their implications in cancer have grasped the attention of the scientific community. Recently, several studies have described the association between miRNA expression profiles and pathological and clinical BC features. Moreover, these molecules represent a new type of molecular marker that can identify prognosis and guide the management of BC patients. With the increasing understanding of miRNA networks and their impact in the biology of BC, as well as the development of viable strategies to modulate specific miRNAs, we could improve the treatment of this disease.  相似文献   

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微小RNA研究进展   总被引:3,自引:0,他引:3  
微小RNA(miRNA)是参与基因转录后水平调控的非编码小分子RNA.人类基因中大约有3%编码miRNAs,而编码蛋白的基因中30%受到miRNAs的调控.miRNAs在多种生物进程中起到关键作用,包括调节发育、细胞增殖、分化和凋亡,相应的miRNAs的表达变化与包括肿瘤在内的多种疾病有关.本文综述miRNAs的生物学及其与肿瘤的联系,并讨论了miRNAs的研究方法.  相似文献   

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微小RNA(microRNA,miRNA)是一类对基因具有调控功能的内源性非编码小分子RNA.目前认为miRNA在多种生物学过程中起着至关重要的作用,包括细胞增殖、分化、凋亡等.近年研究表明miRNA表达异常能导致疾病甚至肿瘤的发生,有类似于抑癌基因或癌基因的功能.因此,对miRNA的进一步研究为肿瘤的诊断和治疗开辟了...  相似文献   

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Work over the last decade has revealed novel regulatory mechanisms in pathological disease states that are mediated by microRNAs and has inspired researchers to begin elucidating the specific roles of miRNAs in the regulation of genes involved in cancer development and progression. Recently, miRNAs have been explored as therapeutic targets and diagnostic markers of cancer. In this paper, we review recent advances in the study of miRNAs involved in tumorigenesis, focusing on miRNA regulation of genes that have been demonstrated to play critical roles in lung cancer development. We discuss miRNA regulation of genes that play critical roles in the process of malignant transformation, angiogenesis and tumor metastasis, the dysregulation of miRNA expression in cancer development, and the development of miRNA-based diagnostics and therapeutics.  相似文献   

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MicroRNAs (miRNAs) are non-coding RNAs that regulate protein expression. Aberrant miRNA expression in cancer has been well documented; miRNAs can act as oncogenes or tumor-suppressor genes, depending on the cellular context and target genes that they regulate, and are involved in tumor progression and metastasis. The potential mechanisms by which miRNAs are involved in tumor aggressiveness include migration, invasion, cell proliferation, epithelial-to-mesenchymal transition, angiogenesis and apoptosis. MiRNAs are involved in various cellular pathways and an miRNA can elicit more than one biological effect in a given cell. Existing data show the potential clinical utility of miRNAs as prognostic and predictive markers for aggressive and metastatic cancers. The stability of miRNAs in formalin-fixed, paraffin-embedded tissues and body fluids is advantageous for biomarker discovery and validation. In addition, miRNAs can be extracted from small biopsy specimens, which is a further advantage. Finally, miRNAs are potential therapeutic agents for personalized cancer management.  相似文献   

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Over the past decade, microRNAs (miRNAs) have become a new paradigm of gene regulation. miRNAs are involved in a wide array of carcinogenic processes. Indeed, increasing evidence has shown the importance of miRNAs in cancer, suggesting their possible use as diagnostic, predictive and prognostic biomarkers, leading to miRNA-based anti-cancer therapies, either alone or in combination with current targeted therapies, with the goal of improving cancer treatment responses and increasing cure rates. The advantage of using a miRNA approach is based on the ability to concurrently target multiple effectors of pathways involved in cell proliferation, migration and survival. This review sheds new light on miRNA regulation of genes that play critical roles in the process of malignant transformation and tumour metastasis, the dysregulation of miRNA expression in cancer development and the development of miRNA-based diagnostics and therapeutics.  相似文献   

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MicroRNAs (miRNAs) are important regulators of gene expression. Alteration of miRNA expression caused by exposure of different carcinogens has been well reported. This review aims to present the miRNAs dysregulated by exposure of different types of carcinogens in different biological systems and to discuss their potential roles in different stages of chemical carcinogenesis, following an introduction of miRNA biogenesis, regulatory mechanisms, and target identification. Available information shows that expression of a large number of miRNAs is readily changed by exposure of carcinogens in tissue- and chemical-specific manners. Carcinogenic agents generally induce many more changes in miRNA expression than non-carcinogenic chemicals. There are many more changes in cancer-target tissues than in the non-target tissues after acute or chronic exposure to carcinogens. Many of the miRNAs deregulated by carcinogens are involved in regulation of genes that are important for every stage of chemical carcinogenesis, including xenobiotic metabolism, carcinogen-induced hypomethylation, DNA repair, apoptosis, cell proliferation, tumor suppression, cell transformation, oncogenesis, tumor angiogenesis, tumor progress, mangliant transformation, and other functions. Many miRNAs function as putative oncogenes and tumor suppressor genes. The carcinogenic functions of carcinogens may be dependent on the balance between tumor-suppressor miRNAs and oncogenic miRNAs. Thus, the miRNA profiles and miRNAs specific to carcinogen exposure have the potential to be used as biomarkers for identifying genotoxicity and carcinogenicity of chemicals and indicating exposure of carcinogens.  相似文献   

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Clear cell RCC is the most common, and more likely to metastasize, of the three main histological types of RCC. Pathologic stage is the most important prognostic indicator and nuclear grade can predict outcome within stages of localized RCC. Epithelial tumors are thought to accumulate a series of genetic and epigenetic changes as they progress through well-defined clinical and histopathological changes. MicroRNAs (miRNAs) are involved in the regulation of mRNA expression from many human genes and miRNA expression is dysregulated in cancer. To better understand the contribution of dysregulated miRNA expression to the progression and biology of ccRCC, we examined the differences in expression levels of 723 human miRNAs through a series of analyses by stage, grade, and disease progression status in a large series of 94 ccRCC. We found a consistent signature that included significant upregulation of miR-21-5p, 142-3p, let-7g-5p, let-7i-5p and 424-5p, as well as downregulation of miR-204-5p, to be associated with ccRCC of high stage, or high grade, or progression. Discrete signatures associated with each of stage, grade, or progression were also identified. The let-7 family was significantly downregulated in ccRCC compared with normal renal parenchyma. Expression of the 6 most significantly differentially expressed miRNAs between ccRCC was verified by stem-loop qRT-PCR. Pathways predicted as targets of the most significantly dysregulated miRNAs included signaling, epithelial cancers, metabolism, and epithelial to mesenchymal transition. Our studies help to further elucidate the biology underlying the progression of ccRCC and identify miRNAs for potential translational application.  相似文献   

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Iorio MV  Croce CM 《Carcinogenesis》2012,33(6):1126-1133
When, ~20 years ago, investigators first determined that components of the genome considered nonfunctional had, in fact, gene regulatory capacity, they probably had no idea of their potential in controlling cell fate and were forced to revise and somehow reorganize their view of the molecular biology. Indeed, it is currently well documented how a class of small non-coding RNAs, microRNAs, are conserved among the species, expressed in different tissues and cell types and involved in almost every biological process, including cell cycle, growth, apoptosis, differentiation and stress response, exerting a finely tuned regulation of gene expression by targeting multiple molecules. As a consequence of the widespread range of processes they are able to influence, it is not surprising that miRNA deregulation is a hallmark of several pathological conditions, including cancer. Indeed, the aberrant expression of these tiny molecules in human tumors is not just a casual association, but they can exert a causal role, as oncogenes or tumor suppressors, in different steps of the tumorigenic process, from initiation and development to progression toward the acquisition of a metastatic phenotype. An increasing body of evidence has indeed proved the importance of miRNAs in cancer, suggesting their possible use as diagnostic, prognostic and predictive biomarkers and leading to exploit miRNA-based anticancer therapies, either alone or in combination with current targeted therapies, with the goal to improve disease response and increase cure rates. Here, we review our current knowledge about miRNA involvement in cancer.  相似文献   

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