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Metabolic Reprogramming of Triple-Negative Breast Cancer: The Role of miRNAs 三阴性乳腺癌的代谢重编程:mirna的作用
Pub Date : 2017-12-20 DOI: 10.1515/MICRNAT-2017-0001
A. Qattan
MicroRNAs (miRNAs) are well known to influence the expression of the genes that regulate critical cellular functions. Various reports have suggested that they play critical roles in breast cancer metabolism through the regulation of various metabolic pathways, including the metabolism of glucose, lipids, glycolysis and the mitochondrial tricarboxylic acid cycle (TCA). miRNAs regulate the metabolic process by targeting key molecules (enzymes, kinases transporters) or by modifying the expression of key transcription molecules. In addition, miRNAs can indirectly regulate mRNA translation by targeting chromatin-remodeling enzymes. Furthermore, miRNAs influence the expression of both oncogenes and tumor suppressors and have a major impact on PI3K/AKT, HIF, and MYC signal transduction, which contributes to the metabolic phenotype in human cancer. Although human epidermal growth factor and endocrine therapies have been effective in treating breast cancer, for locally advanced and distant metastases mortality remains high. Drug resistance and recurrence remain major hurdles for advanced breast cancer therapy. Given the critical influence of metabolic reprogramming in the progression of neoplasm, tumorigenesis and metastasis, research should focus on novel targets of metabolic enzymes to reverse drug resistance and improve overall survival rates. Blocking the miRNAs that contribute to metabolic reprogramming or the use of exogenous miRNAs as antisense oligonucleotides, may be an effective way to treat aggressive, chemo-resistant cancers. This review summarizes current knowledge on the mechanism of Research Article
众所周知,MicroRNAs (miRNAs)可以影响调节关键细胞功能的基因的表达。各种报道表明,它们通过调节各种代谢途径,包括葡萄糖、脂质、糖酵解和线粒体三羧酸循环(TCA)的代谢,在乳腺癌代谢中发挥关键作用。mirna通过靶向关键分子(酶、激酶转运体)或通过修改关键转录分子的表达来调节代谢过程。此外,mirna可以通过靶向染色质重塑酶间接调节mRNA的翻译。此外,mirna影响癌基因和肿瘤抑制因子的表达,并对PI3K/AKT、HIF和MYC信号转导产生主要影响,这有助于人类癌症的代谢表型。虽然人表皮生长因子和内分泌疗法在治疗乳腺癌方面是有效的,但对于局部晚期和远处转移的死亡率仍然很高。耐药和复发仍然是晚期乳腺癌治疗的主要障碍。鉴于代谢重编程在肿瘤进展、肿瘤发生和转移中的重要作用,研究应关注代谢酶的新靶点,以逆转耐药和提高总体生存率。阻断参与代谢重编程的mirna或使用外源性mirna作为反义寡核苷酸,可能是治疗侵袭性耐药癌症的有效方法。本文对研究文章的机制进行了综述
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引用次数: 4
Exosomic microRNAs as emerging key regulators of intercellular communication in the tumor microenvironment and beyond 外泌体microrna在肿瘤微环境及其他环境中作为细胞间通讯的关键调节因子
Pub Date : 2016-01-21 DOI: 10.1515/MICRNAT-2016-0001
M. Murtadha, M. Fabbri
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引用次数: 0
microRNA-based diagnostic and therapeutic opportunities in lung cancer 基于微rna的肺癌诊断和治疗的机会
Pub Date : 2015-04-29 DOI: 10.2478/MICRNAT-2014-0006
Jianfei Zhao, Yan Cai, Xi Liu
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引用次数: 0
MicroRNAs are central to osteogenesis: a review with a focus on cardiovascular calcification microrna是骨形成的核心:综述与心血管钙化的重点
Pub Date : 2015-03-24 DOI: 10.2478/MICRNAT-2014-0005
S. Coffey, Gregory T. Jones
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引用次数: 2
miRNA function and modulation in stem cells and cancer stem cells miRNA在干细胞和肿瘤干细胞中的功能和调控
Pub Date : 2014-12-17 DOI: 10.2478/MICRNAT-2014-0004
A. Decastro, J. Direnzo
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引用次数: 1
From life to death: microRNAs in the fine tuning of the heart 从生到死:心脏微调中的微rna
Pub Date : 2014-12-12 DOI: 10.2478/MICRNAT-2014-0003
Sayantan Nath, S. Rizvi, Munish Kumar
The heart is one of the most important vital organs, and any malfunctioning of the heart and its blood vessels may contribute to cardiovascular disorders. Diseases of the cardiovascular system represent the most common cause of human morbidity and mortality around the globe. Thus, there is always a need for innovative new therapies and diagnostics for cardiovascular disorders. In the past decades, a plethora of tiny, endogenous, single- stranded RNA sequences called microRNAs (miRNAs) has been studied meticulously in cardiovascular development and pathophysiology, providing a new dimension to the heart's biology. miRNAs posttranscriptional inhibit the gene expression of specific mRNA targets through Watson- Crick base pairing between the miRNA "seed region" and the 3' untranslated regions (UTRs) of target mRNAs. Better recognized as "master switches", miRNAs are emerging as vital regulators of mammalian cardiovascular development and disease and thus are helpful in understanding therapeutic targets and diagnostics for a variety of cardiovascular disorders. In this review, a detailed discussion of the roles of various microRNAs in cardiovascular development and pathophysiology with potential therapeutics is considered.
心脏是最重要的生命器官之一,心脏及其血管的任何功能失常都可能导致心血管疾病。心血管系统疾病是全球人类发病和死亡的最常见原因。因此,总是需要对心血管疾病进行创新的新疗法和诊断。在过去的几十年里,大量微小的内源性单链RNA序列被称为microRNAs (miRNAs),在心血管发育和病理生理学中得到了细致的研究,为心脏生物学提供了一个新的维度。miRNAs转录后通过miRNA“种子区”与靶mRNA的3′非翻译区(UTRs)之间的Watson- Crick碱基配对抑制特定mRNA靶点的基因表达。作为“主开关”,mirna正在成为哺乳动物心血管发育和疾病的重要调节因子,因此有助于了解各种心血管疾病的治疗靶点和诊断。在这篇综述中,详细讨论了各种microrna在心血管发展和病理生理中的作用,并考虑了潜在的治疗方法。
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引用次数: 0
Circulating MicroRNAs as Biomarkers in Coronary Heart Disease and Heart Failure 循环microrna作为冠心病和心力衰竭的生物标志物
Pub Date : 2014-09-12 DOI: 10.2478/MICRNAT-2014-0002
V. Cameron, A. Pilbrow
MicroRNAs (miRNAs) are small non-coding, single-stranded RNAs (19-25 nucleotides long) that regulate expression of multiple target genes, predominantly by binding to the 3' untranslated region of messenger RNA (mRNA) transcripts, resulting either in translational inhibition or mRNA degradation. miRNAs are found in many bodily fluids, including plasma and serum, and are protected from degradation in the circulation through association with lipids, proteins, or microparticles, making them attractive disease biomarker candidates. Circulating levels of cardiac miRNAs (including miR-1, miR-133a, miR-208a, miR-208b, and miR-499) have been frequently reported as elevated in both coronary heart disease (CHD) and heart failure (HF) and have been proposed as candidate biomarkers that reflect the severity of myocardial injury. Subsequent large, array-based screening studies comparing patients and controls have identified altered expression of additional miRNAs, not just those of cardiac origin. However, among these studies there has been little consensus as to which miRNAs are top candidates for diagnosis or prognosis in either CHD or HF. The measurement of circulating miRNAs is further complicated by the timing of collection, especially after acute cardiac events while miRNA levels in blood may be rapidly changing; confounding influences from medications or contaminating blood cells at the time of sampling; and the need for standardization of normalization strategies. This review evaluates recent developments in the identification of circulating miRNAs as markers for diagnosis and prognosis in CHD and HF, and the methodological issues in measurement of circulating miRNAs. Research Article
MicroRNAs (miRNAs)是一种小的非编码单链RNA(长19-25个核苷酸),主要通过结合信使RNA (mRNA)转录物的3'非翻译区来调节多个靶基因的表达,从而导致翻译抑制或mRNA降解。mirna存在于包括血浆和血清在内的许多体液中,并通过与脂质、蛋白质或微粒的结合而免受循环中的降解,使其成为有吸引力的疾病生物标志物候选者。心脏mirna的循环水平(包括miR-1、miR-133a、miR-208a、miR-208b和miR-499)在冠心病(CHD)和心力衰竭(HF)中经常被报道升高,并被认为是反映心肌损伤严重程度的候选生物标志物。随后的大型阵列筛选研究比较了患者和对照组,发现了其他mirna的表达改变,而不仅仅是心脏来源的mirna。然而,在这些研究中,对于哪些mirna是CHD或HF的诊断或预后的首选候选,几乎没有共识。循环miRNA的测量因收集时间而进一步复杂化,特别是在急性心脏事件发生后,血液中的miRNA水平可能会迅速变化;抽样时药物或污染血细胞的混杂影响;以及标准化策略的必要性。这篇综述评估了循环mirna作为冠心病和心衰诊断和预后标记物的鉴定的最新进展,以及循环mirna测量的方法问题。研究文章
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引用次数: 2
Can miRNA Biomarkers Be Utilized to Improve the Evaluation and Management of Pancreatic Cystic Lesions miRNA生物标志物能否用于改善胰腺囊性病变的评估和管理
Pub Date : 2014-01-01 DOI: 10.2478/MICRNAT-2013-0003
Linda S. Lee, A. E. Szafranska-Schwarzbach, B. Andruss, D. Conwell
Received 03 June 2013 Accepted 14 July 2013 Abstract This article reviews the current strategies and challenges of diagnosing pancreatic cystic lesions, and presents an overview of molecular tools that are available to enhance diagnostic accuracy. Specifically, we highlight the emergence of microRNAs (miRNAs) as diagnostic markers. miRNA signatures have been reported for both solid tissue and biofluid specimens, including cyst fluid, collected from patients with solid and cystic pancreatic lesions. These miRNA signatures offer the opportunity to improve molecular characterization of pancreatic lesions, to help guide clinical management through early diagnosis and informed prognosis, and to provide novel therapeutic targets for pancreatic cancer.
摘要本文回顾了目前胰腺囊性病变诊断的策略和挑战,并概述了可用于提高诊断准确性的分子工具。具体来说,我们强调了microRNAs (miRNAs)作为诊断标记物的出现。据报道,从实性和囊性胰腺病变患者收集的实体组织和生物液标本(包括囊肿液)中均存在miRNA特征。这些miRNA特征提供了改善胰腺病变分子特征的机会,通过早期诊断和知情预后帮助指导临床管理,并为胰腺癌提供新的治疗靶点。
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引用次数: 1
Diet-Derived MicroRNAs: Separating the Dream from Reality 饮食衍生的microrna:将梦想与现实分离
Pub Date : 2014-01-01 DOI: 10.2478/MICRNAT-2014-0001
K. Cottrill, S. Y. Chan
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引用次数: 14
In situ hybridization-based detection of microRNAs in human diseases 基于原位杂交技术检测人类疾病中的microrna
Pub Date : 2014-01-01 DOI: 10.2478/MICRNAT-2013-0002
Xinna Zhang, Xiongbin Lu, G. Lopez-Berestein, A. Sood, G. Calin
Received 05 March 2013 Accepted 31 May 2013 Abstract MicroRNAs (miRNAs) are small non-coding RNAs that regulate various aspects of gene expression in physiology and development. Links between miRNAs and the initiation and progression of human diseases are becoming increasingly apparent. The development of methods to detect the subcellular and tissue localization of miRNAs is essential for understanding their biological role in homeostasis. In this review, we discuss how in situ hybridization can complement tissuelevel miRNA expression profiling and its role as an investigational tool to better understand the etiology of human diseases. Furthermore, in situ hybridization of miRNAs represents a potent diagnostic assay that could be further refined and utilized for clinical applications.
摘要MicroRNAs (miRNAs)是一种小的非编码rna,在生理和发育过程中调节基因表达的各个方面。mirna与人类疾病的发生和发展之间的联系正变得越来越明显。发展检测mirna的亚细胞和组织定位的方法对于了解它们在体内平衡中的生物学作用至关重要。在这篇综述中,我们讨论了原位杂交如何补充组织水平miRNA表达谱及其作为研究工具的作用,以更好地了解人类疾病的病因。此外,mirna的原位杂交是一种有效的诊断方法,可以进一步完善并用于临床应用。
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引用次数: 12
期刊
microRNA diagnostics and therapeutics
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