从病毒性肝炎到肝细胞癌：外泌体microRNA的作用

外泌体是一种纳米级的磷脂双分子层小囊泡,内含丰富而复杂的生物分子,如DNA、mRNA、microRNA(miRNA)、脂质和蛋白质。外泌体可由大多数种类细胞分泌和摄取,通过细胞间运输的方式完成信息传递。外泌体被受体细胞摄取后,释放其中所含生物活性物质,用以调节受体细胞生物过程,如促进肿瘤的生长和转移。外泌体及其内容物的变化与多种疾病有着重要联系。近年来,关于外泌体miRNA在病毒性肝炎所致肝细胞癌(HCC)发生发展中的作用已经受到广泛关注,并且不同来源的外泌体miRNA在此过程中发挥的作用也有所不同。本文简要回顾了外泌体miRNA在病毒性肝炎相关HCC发生发展中的作用研究,并提出外泌体miRNA可能是针对HCC微环境的免疫治疗靶点。     

外泌体源性的微小RNA在肝癌中的研究进展

肝癌是常见的恶性消化道肿瘤,外泌体是由各种体液分泌的膜性囊泡,其中包含有脂质、核酸、微小RNA、长链非编码RNA等多种物质.外泌体包裹下的miRNA拥有更好的生物稳定性.研究发现肿瘤细胞较正常细胞能分泌更多的外泌体,肿瘤细胞来源的外泌体中miRNA在肿瘤的进展、转移、耐药等多个方面起重要作用.本文阐述了外泌体源性的mi...     

外泌体源性miRNA:心血管疾病新的生物标志物

正外泌体是一类大小约30~100 nm具有脂双层膜的囊状结构,内含来源于分泌细胞的蛋白质、microRNA(miRNA)、circular RNA(crcRNA)、mRNA、DNA等生物分子~([1])。细胞将miRNA浓集在一起,包装进外泌体,而后外泌体被释放到细胞间隙。外泌体内包裹的miRNA与相关蛋白复合物一起到达临近或远端细胞内。miRNA进入受体细胞后,可沉默靶基因,从而调节受体细胞功能。由于外泌体在细胞通讯方面呈现出与传统细胞通讯途径不同的一种独     

外泌体来源微小RNA在心血管疾病中作用研究进展

在不同的病理生理状态下,细胞可分泌包含有特定内含物的外泌体至细胞外环境中。其中,来源于外泌体的微小RNA(miRNA)能够参与细胞间的物质传递和信号转导。近年来,人们逐渐认识到外泌体及其相关的miRNA在心血管疾病发病过程中的重要作用。本文介绍了外泌体的基本特征及外泌体来源的miRNA的生物学特性,讨论了外泌体来源的miRNA在不同心血管疾病中的表达情况。     

外泌体MicroRNA在部分肺部疾病中的研究进展

外泌体(Exosomes)是由细胞产生的具有生物活性的纳米级载体,普遍存在于大多数体液中。外泌体中富含的微小RNA(microRNA,miRNA)称为外泌体miRNA,它是一种多功能非编码RNA,对基因调节至关重要。外泌体miRNA在细胞间物质和信号转递中至关重要,参与炎症、细胞增殖、分化和凋亡等多种生物学过程,从而可能调节多种病理过程。外泌体已被视为当前研究的热点。最近的研究发现,外泌体miRNA在肺部疾病的发病机理中具有重要意义。本文旨在综述有关外泌体miRNA在慢性阻塞性肺疾病(慢阻肺)、哮喘、特发性肺纤维化(IPF)和肺结核等常见肺部疾病中的研究进展。     

外泌体对胰腺癌的诊疗价值及应用前景

外泌体是一种由多种细胞分泌的直径为30~100nm的内源性囊泡,是细胞内的多泡体(MVB)与胞浆膜融合的产物,通过胞吐作用释放至细胞外隙或生物体液中。因外泌体含有蛋白质、信使RNA(mRNA)、微RNA(miRNA)等生物信息,故可参与胰腺癌的多种生理及病理过程,如促进肿瘤生长与迁移、修复损伤组织等,进而为胰腺癌的早期诊断及预后判断提供一种新的方式。该文就外泌体对胰腺癌的诊疗及预后判断等方面的潜在价值及应用前景作一综述。     

外泌体在消化系统肿瘤中的研究进展

近年来,消化系统肿瘤的高发病率和高病死率已引起国内外学者的广泛关注。外泌体作为一种可以包裹药物的载体,目前已被应用于肿瘤的靶向治疗。研究表明,外泌体可以携带蛋白质和miRNA在细胞之间转运,可作为肿瘤标志物,并且可以作为消化系统肿瘤治疗药物运输的载体,诱导抗肿瘤免疫反应,从而在促进消化系统肿瘤的发展、侵袭转移中发挥重要的作用。     

心力衰竭患者血浆外泌体microRNA检测及其功能分析

目的明确心力衰竭(心衰)患者血浆外泌体microRNA(miRNA)表达谱的差别,寻找其在心衰早期诊断和预后评估中的价值。方法应用外泌体提取试剂盒抽提10例心衰患者及10例非心衰对照者外周血浆外泌体,对血浆外泌体miRNA进行高通量测序,初步筛选差异表达miRNA,并通过实时荧光定量PCR方法验证,分析差异表达miRNA的功能及其与NT-proBNP的相关性。结果 miRNA高通量测序共筛选出24条显著差异表达的血浆外泌体miRNA。其中14条miRNA表达显著上调,10条miRNA表达明显下调。定量PCR验证和高通量测序筛选结果一致。差异表达miRNA的功能涉及炎性反应、细胞凋亡、增值、自噬等。相关性分析提示miR-122-5p与NT-proBNP具有相关性(r=0.537,P=0.015)。结论血浆外泌体来源miRNA可能成为潜在的辅助诊断心力衰竭和评估预后的一类新型生物标志物。     

外泌体microRNA在血管老化及其相关性疾病中的作用

血管老化是指血管结构和功能随增龄而发生的退行性改变,其影响多种疾病的发生、进展和预后。血管内皮细胞和血管平滑肌细胞是构成血管壁的主要细胞,是血管老化的重要细胞生物学基础。近年来,外泌体微小RNA(miRNA)与血管老化的关系成为研究热点。本综述将总结外泌体miRNA在血管内皮细胞和平滑肌细胞衰老过程中的作用,同时讨论外泌体miRNA在血管老化相关性疾病中的功能。     

关于外泌体在心血管疾病中作用研究的进展

外泌体是一种被大多数细胞分泌的双层脂质囊泡,内含丰富的蛋白质、脂类、核酸.它能介导细胞间的信息传递和交换,是细胞信息传递的关键介质.近年来,越来越多的研究发现外泌体,尤其是外泌体微小RNA (mi-croRNA,miRNA)可抑制炎症、减少细胞凋亡、参与多种心血管疾病的调节.现就外泌体的基本特征、在心血管疾病中的诊断意...     

Pancreatic cancer diagnosis by free and exosomal miRNA

Patients with pancreatic adenocarcinoma (PaCa) have a dismal prognosis. This is in part due to late diagnosis prohibiting surgical intervention, which provides the only curative option as PaCa are mostly chemo- and radiation resistance. Hope is raised on a reliable non-invasive/minimally invasive diagnosis that is still missing. Recently two diagnostic options are discussed, serum MicroRNA (miRNA) and serum exosomes. Serum miRNA can be free or vesicle-, particularly, exosomes-enclosed. This review will provide an overview on the current state of the diagnostic trials on free serum miRNA and proceed with an introduction of exosomes that use as a diagnostic tool in serum and other body fluids has not received sufficient attention, although serum exosome miRNA in combination with protein marker expression likely will increase the diagnostic and prognostic power. By their crosstalk with host cells, which includes binding-initiated signal transduction, as well as reprogramming target cells via the transfer of proteins, mRNA and miRNA exosomes are suggested to become a most powerful therapeutics. I will discuss which hurdles have still to be taken as well as the different modalities, which can be envisaged to make therapeutic use of exosomes. PaCa are known to most intensely crosstalk with the host as apparent by desmoplasia and frequent paraneoplastic syndromes. Thus, there is hope that the therapeutic application of exosomes brings about a major breakthrough.     

Characteristics of the MicroRNA Expression Profile of Exosomes Released by Vero Cells Infected with Porcine Epidemic Diarrhea Virus

Exosomes are nanoscale vesicles actively secreted by a variety of cells. They contain regulated microRNA (miRNA), allowing them to function in intercellular communication. In the present study, the role of exosomal miRNAs in porcine epidemic diarrhea virus (PEDV) infection was investigated using exosomes isolated from Vero cells infected with PEDV. The results of transmission electron microscopy observation showed that the exosomes are spherical in shape, uniform in size, and negatively stained in the membrane. Nanoparticle tracking analysis showed that the average exosome particle size is 130.5 nm. The results of miRNA sequencing showed that, compared with the control group, a total of 115 miRNAs are abnormally expressed in the exosomes of infected cells. Of these, 80 miRNAs are significantly upregulated and 35 miRNAs are significantly downregulated. Functional annotation analysis showed that the differentially expressed miRNAs are associated with PEDV infection through interaction with the cAMP, Hippo, TGF-beta, HIF-1, FoxO, MAPK, and Ras signaling pathways. Thus, our findings provide important information about the effects of PEDV infection on exosomal miRNA expression and will aid the search for potential anti-PEDV drug candidates.     

Exosomal microRNA-25 released from cancer cells targets SIK1 to promote hepatocellular carcinoma tumorigenesis

BackgroundHepatocellular carcinoma (HCC) is recognized as a leading cause of cancer-associated fatality worldwide. Our study here aimed to probe the mechanism by which exosomes secreted by CSQT-2, an HCC cell line, affected the progression of HCC.MethodsExosomes were extracted from CSQT-2 cells. Colony formation, Transwell, sphere formation and flow cytometric analyses were applied to assess cell biological activities. Microarray analysis detected the change of microRNA (miRNA) expression after exosome treatment, followed by RT-qPCR validation. Luciferase reporter was applied to detect the binding between SIK1 and miR-25. Xenograft studies in nude mice manifested tumor growth and metastatic ability of miR-25 and SIK1.ResultsThe exosome treatment enhanced cell malignant phenotype in vitro and tumor growth and liver and lung metastases in vivo. The exosomes elevated miR-25 expression in HCC cells. miR-25 targeted SIK1 which was decreased in the exosomes-treated cells. miR-25 inhibitor reduced cell malignant phenotype and attenuated tumorigenesis and metastasis in vivo. SIK1 silencing reversed the effect of miR-25 inhibitor. The exosome treatment potentiated the Wnt/β-catenin pathway in cells, whereas miR-25 inhibitor blunted the pathway activity.ConclusionMiR-25 shuttled through CSQT-2-derived exosomes promoted the development of HCC by reducing SIK1 expression and potentiating the Wnt/β-catenin pathway.     

Adipose may actively delay progression of NAFLD by releasing tumor‐suppressing,anti‐fibrotic miR‐122 into circulation

Nonalcoholic fatty liver disease (NAFLD) is the most common liver pathology. Here we propose tissue‐cooperative, homeostatic model of NAFLD. During early stages of NAFLD the intrahepatic production of miR‐122 falls, while the secretion of miRNA‐containing exosomes by adipose increases. Bloodstream carries exosome to the liver, where their miRNA cargo is released to regulate their intrahepatic targets. When the deterioration of adipose catches up with the failing hepatic parenchyma, the external supply of liver‐supporting miRNAs gradually tapers off, leading to the fibrotic decompensation of the liver and an increase in hepatic carcinogenesis. This model may explain paradoxical observations of the disease‐associated decrease in intrahepatic production of certain miRNAs with an increase in their levels in serum. Infusions of miR‐122 and, possibly, some other miRNAs may be efficient for preventing NAFLD‐associated hepatocellular carcinoma. The best candidates for exosome‐wrapped miRNA producer are adipose tissue‐derived mesenchymal stem cells (MSCs), known for their capacity to shed large amounts of exosomes into the media. Notably, MSC‐derived exosomes with no specific loading are already tested in patients with liver fibrosis. Carrier exosomes may be co‐manufactured along with their cargo. Exosome‐delivered miRNA cocktails may augment functioning of human organs suffering from a variety of chronic diseases.     

肝癌外泌体源性miRNA表达及其临床价值

肝细胞癌(HCC)早期诊断和有效治疗,仍然是困扰医学界的难题。外泌体是直径为40~100 nm的微小囊泡,内含蛋白质、脂质和核酸,作为信息物质交换的转运载体,在调控生物分子功能、维持细胞内环境中起重要作用。HCC外泌体功能包括胞间信息交换、新血管生成、癌细胞转移与多药耐药等,可介导微小RNA(miRNA)转化以调控肿瘤进展的微环境,进而影响癌细胞的病理生理学行为。外泌体源性miRNA可用于HCC监测或为早期诊断潜在特异标志物,且可作为HCC治疗靶目标,具有开发应用前景。现综述HCC外泌体源性miRNA研究的新进展。     

细胞外囊泡微小RNA在动脉粥样硬化中的作用研究进展

细胞外囊泡(EV)是脂质双层包裹的微型囊泡,广泛存在于各种生物体液中,并可通过转运多种生物活性物质调节细胞的分子通路和生物学行为,特别是微小RNA(miRNA)。近年研究发现细胞外囊泡中的miRNA在动脉粥样硬化的发生和发展中发挥重要的调节作用。本文综述了动脉粥样硬化时细胞外囊泡miRNA转移的选择性及其在动脉粥样硬化发展过程中的调控作用和在诊断治疗中的潜在应用前景。     

MiRNA在动脉粥样硬化血管新生中的作用

在动脉粥样硬化斑块的发展过程中,血管新生是一个重要的影响因素,局部新生血管和斑块稳定性密切相关。随着斑块内新生血管数量的增加,斑块内脂质和各种炎细胞堆积,最终导致基质降解,纤维帽变薄,斑块破裂,进而引发严重的心血管事件。mi RNA的研究越发地让我们认识到,mi RNA不仅在肿瘤疾病领域,在动脉粥样硬化领域中也发挥着极其重要的作用。近年来,在心血管系统中发现多种可能与动脉粥样硬化相关的mi RNA,可能为动脉粥样硬化的早期诊断和治疗选择提供了新的线索。     

miRNA与肿瘤转移调控机制的研究进展

转移是恶性肿瘤的基本特征和重要标志,也是癌症患者治疗失败或死亡的首要原因。微小核糖核酸[micro ribonucleic acid(microRNA,miRNA)]是一类具有调控功能的非编码RNA片段,通过调控下游靶基因的转录和翻译,在肿瘤发生发展过程中发挥重要作用。miRNA参与恶性肿瘤侵袭及转移生物学行为中的多个重要环节,阐明肿瘤转移相关miRNA的转移调控机制,将为我们认识肿瘤发生发展提供新视角,给癌症的诊断和治疗带来新突破。该文对miRNA与肿瘤转移调控机制的研究进展进行综述。     

MicroRNAs potential utility in colon cancer: Early detection,prognosis, and chemosensitivity

Over the past decade, research has shown that aberrant expression of microRNA (miRNA) is involved in colorectal cancer development and progression. MicroRNAs are small sequences of non-coding RNA that regulate expression of genes involved in important cellular functions, such as cell differentiation, multiplication, and apoptosis. A specific miRNA may display the effects of a tumor suppressor or oncogene. Altered miRNA expression is found in colorectal cancer (CRC) and patterns of miRNA expression correlate with CRC detection and outcome. Studies also have examined the use of circulating serum miRNA and fecal miRNA expression as non-invasive markers for early detection. Here, we review recent evidence demonstrating the potential role of miRNA in CRC and the implications of its use in the diagnosis, prognosis, and management of CRC.     

miRNA与肺癌关系的研究进展

miRNA是一类内源性高度保守的非编码小RNA,长度约22nt,主要通过转录后机制调控靶基因的翻译或表达,在细胞的增殖、凋亡、肿瘤的发生发展等多种生理和病理过程中发挥重要作用.随着我们对miRNA的认识不断增加,对其与肺癌关系的研究也不断深入,将为肺癌的诊断、治疗及预后等方面提供新线索.