环状RNA在肝细胞癌发生发展及诊疗中的作用

肝细胞癌(HCC)作为原发性肝癌最常见的类型,是一种具有侵袭性且致命的恶性肿瘤,其发生发展是一个多基因参与、多步骤、多阶段的过程。环状RNA(circRNA)作为一类内源性非编码RNA,主要通过吸附微小RNA(miRNA)或者RNA结合蛋白(RBP)发挥“海绵作用”,进而调控下游靶基因表达。本文全面介绍了circRNA在HCC信号转导、免疫、代谢、耐药、HBV相关HCC中的作用及意义,及其作为HCC的生物标志物或治疗靶点的潜在价值,为HCC的诊断和治疗提供新思路。     

环状RNA在食管癌诊断和预后中的研究进展

环状RNA(circular RNA,circRNA)是一种新型内源性环状结构的非编码RNA,受顺式调控元件和相关蛋白反式调控,经“反向剪接”机制产生。circRNA在基因剪接、转录、染色质修饰、miRNA海绵作用及蛋白捕获等方面发挥重要作用。circRNA高度稳定,且在不同组织中差异表达。circRNA异常表达与肿瘤发生和转移相关。然而,食管癌中具有重要功能的circRNA及作用机制目前尚不清楚。本文结合circRNA的功能特点,对circRNA在食管癌发生发展中的作用及其作为食管癌诊断、预后分子标志物的研究进展做一综述。     

心血管疾病相关circRNA调控机制的研究进展

环状RNA(circRNA)是不同于传统线性RNA的一类新型非编码RNA,以共价键形成封闭环状结构,在细胞中更加稳定。许多研究证明circRNA在基因表达中发挥了重要的调控作用,特别是有miRNA海绵体作用,随着对circRNA研究的日益增多,发现其与许多循环系统疾病的发生、发展密切相关。因此,circRNA有望成为心血管疾病早期诊断及治疗靶点的重要生物标志物。本文总结了关于circRNA的性质及功能以及其在心血管疾病中的调控作用。     

环状RNA在肝细胞癌发生发展调控及诊断治疗中的作用研究进展

肝细胞癌（HCC）是消化系统的常见恶性肿瘤,临床治疗效果及预后较差。环状RNA(circRNA)是近几年非编码RNA研究领域中的新兴热点之一,可以通过调控HCC的肿瘤干细胞干性维持、细胞周期、细胞凋亡及肿瘤血管生成等多个生物学进程而影响HCC的发生及进展。由于circRNA有一定保守性且具有特殊的闭环结构使得它们在真核生物的血液、唾液、尿液等体液中较为稳定,具有作为HCC的诊断标志物及治疗靶点的潜在可能。同时,circRNA还通过多种机制参与HCC耐药并调节HCC细胞对抗癌药物的反应程度。     

环状RNA在消化系统疾病中的研究进展

环状RNA(circular RNA,circRNA)是一种共价闭合的环状非编码RNA,广泛存在于真核细胞中,具有结构稳定、高保守性及细胞组织特异性和发育阶段特异性等特征。这些特征赋予了circRNA许多潜在作用,如作为miRNA海绵调控靶miRNA的活性,并参与基因转录和蛋白生成的调控。越来越多的研究发现,circRNA在多种疾病的发生、发展中起着重要作用,并且在某些疾病的诊断治疗等方面具有巨大的潜能,有望成为疾病诊断的生物标志物或疾病治疗的靶点。本文就circRNA在消化系统疾病中的研究进展作一概述,探讨其在消化系统疾病诊断和治疗中的潜在临床应用。     

环状RNA在消化系统肿瘤中作用的研究进展

环状RNA(circRNA)是一类广泛存在于多种细胞中的非编码RNA(ncRNA),其在不同物种间高度保守,可充当微RNA(miRNA)海绵,调控基因表达。越来越多的研究表明circRNA在消化系统肿瘤发生、发展中发挥重要作用,可作为肿瘤诊断的生物标记物和评估预后的指标,但其功能仍需更深入的研究来验证。本文就circRNA在消化系统肿瘤中作用的研究进展作一综述。     

环状RNA与自身免疫性疾病

环状RNA(circRNA)是形成共价闭合的RNA环的非编码RNA,circRNA的发现揭示了转录后基因表达调控的新的层面。目前对circRNA功能的认知虽然有限,但已发现的一些关于circRNA的信息已显示出其具有吸附微小RNA (miRNA)的海绵作用和调节基因表达的作用。目前报道得最清楚的是关于circRNA CDR1as可作为miR-7的海绵的研究。miRNA在自身免疫性疾病的发病及进程中起着重要的作用,而circRNA又可作为海绵吸附miRNA,具有基因表达调控的作用,因此circRNA与自身免疫性疾病密切相关并且可能成为自身免疫性疾病的潜在治疗靶点。未来的研究可深入探究circRNA和自身免疫性疾病之间的关系。本文对circRANs的识别和功能进行综述,并介绍circRNA与人类疾病之间的关联,探索circRNA在自身免疫性疾病的潜在作用。     

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。     

环状RNA的功能及其在甲状腺乳头状癌中的作用

环状RNA(circRNA)是一种新型的长链非编码RNA(ncRNA),具有共价闭环的特征,不受RNA外切酶影响,相较线性RNA更加稳定。研究表明,circRNA在调节细胞的生理病理过程中具有小分子RNA(miRNA)的海绵效应、调控基因剪接和转录、充当自噬调节剂与RNA结合蛋白的相互作用、翻译蛋白质等重要作用。甲状腺...     

环状RNA的研究现状及展望

环状RNA（circular RNA,circRNA）或称环形RNA,是新近确认的一类特殊的非编码RNA（non-coding RNA,ncRNA）分子,是继microRNA （miRNA）后RNA家族的一颗极具发展潜力的正在升起的新星,也是RNA领域最新的研究热点,方兴未艾.通过与疾病关联的miRNA相互作用,circRNA在疾病中发挥着重要的调控作用,有巨大潜力成为新型的临床诊断标志物.     

Involvement of the circular RNA/microRNA/glucose-6-phosphate dehydrogenase axis in the pathological mechanism of hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is the third most common cause of cancer-related death worldwide with high mortality. The incidence of HCC is increasing in China. Abnormal activation of glucose-6-phosphate dehydrogenase (G6PD) exists in all malignant tumors, including HCC, and is closely related to the development of HCC. In addition, the differential expression of non-coding RNAs is closely related to the development of HCC. This systematic review focuses on the relationship between G6PD, HCC, and non-coding RNA, which form the basis for the circRNA/miRNA/G6PD axis in HCC. The circular RNA (circRNA)/microRNA (miRNA)/G6PD axis is involved in development of HCC. We proposed that non-coding RNA molecules of the circRNA/miRNA/G6PD axis may be novel biomarkers for the pathological diagnosis, prognosis, and targeted therapy of HCC.     

环状RNA在动脉粥样硬化中的研究进展

环状RNA(circRNA)是一类新型内源性非编码RNA,广泛存在于真核生物体中,因其含量丰富、序列保守、结构稳定等特性,是近年来热门的基因表达调节因子。越来越多的研究表明circRNA在影响内皮完整性、血管平滑肌细胞和免疫炎症细胞的功能,以及在驱动动脉粥样硬化(As)斑块起始和稳定中发挥重要作用,因此其可能作为As新型诊断生物标志物和治疗靶标。因此,文章就circRNA在As中研究现状,综述其在As中的功能以及调节机制。     

非编码RNA在卵巢癌中的研究现状

细胞内存在成千上万种非编码RNA(non-coding RNA,ncRNA),人们对ncRNA的认识从最初的转录垃圾已转变为功能调控分子。ncRNA参与介导细胞过程,包括染色质重构、转录、转录后修饰,在许多疾病中扮演着关键调控因子,特别是在恶性肿瘤中可作为致癌因子和抑癌因子驱动特定的细胞生物活动。迄今为止,卵巢癌的发病病因尚不明确,探索ncRNA在卵巢癌细胞中的作用及机制,有助于为卵巢癌的研究提供新的思路。现就卵巢癌相关的ncRNA的研究现状,尤其是微小RNA(miRNA)、长链非编码RNA(lncRNA)及环状RNA(circRNA)作一综述。     

冠心病相关环状RNA调控机制及治疗的研究进展

环状RNA（circRNA）是一种非编码RNA,具有靶向调节小RNA（miRNA）或信使RNA（mRNA）的功能,参与动脉粥样硬化、免疫反应、血管新生、细胞凋亡、细胞增殖、细胞衰老和细胞自噬等多种冠心病（CHD）病理机制。基于circRNA构建的circRNA/miRNA/mRNA交互网络,有助于系统地、动态地反映CHD的发生发展。同时,通过药物干预或人工过表达/敲低circRNA的异常表达,以及circRNA序列编辑等方法,circRNA为今后CHD的靶向和精准治疗提供了新靶点和新策略。尽管如此,目前有关CHD的circRNA调控机制和治疗研究仍处于初级阶段,明确CHD circRNA生物标志物和治疗靶点仍任重而道远。     

环状RNA:心肌缺血/再灌注损伤干预研究新进展

环状RNA（circular RNA,circRNA）是一类新型的内源性非编码RNA,其结构是以其3'端和5'端间以共价键形式相连接而形成的一种circRNA。其因结构稳定、分布广泛、组织表达具有特异性和时序性而备受科学工作者的关注。研究表明circRNA在心肌缺血/再灌注损伤中充当着重要角色,可能作为缺血/再灌注损伤潜在的治疗靶点和生物标志物。本文就circRNA形成的途径、功能和在心肌缺血/再灌注损伤中的作用机制以及中医相关方面进行综述。     

Circular RNA hsa_circ_0098181 inhibits metastasis in hepatocellular carcinoma by activating the Hippo signaling pathway via interaction with eEF2

Introduction and ObjectivesThe development of hepatocellular carcinoma (HCC) is a multi-step process that accumulates genetic and epigenetic alterations, including changes in circular RNA (circRNA). This study aimed to understand the alterations in circRNA expression in HCC development and metastasis and to explore the biological functions of circRNA.Materials and MethodsTen pairs of adjacent chronic hepatitis tissues and HCC tissues from patients without venous metastases, and ten HCC tissues from patients with venous metastases were analyzed using human circRNA microarrays. Differentially expressed circRNAs were then validated by quantitative real-time PCR. In vitro and in vivo assays were performed to assess the roles of the circRNA in HCC progression. RNA pull-down assay, mass spectrometry analysis, and RNA-binding protein immunoprecipitation were conducted to explore the protein partners of the circRNA.ResultsCircRNA microarrays revealed that the expression patterns of circRNAs across the three groups were significantly different. Among these, hsa_circ_0098181 was validated to be lowly expressed and associated with poor prognosis in HCC patients. Ectopic expression of hsa_circ_0098181 delayed HCC metastasis in vitro and in vivo. Mechanistically, hsa_circ_0098181 sequestered eukaryotic translation elongation factor 2 (eEF2) and dissociated eEF2 from filamentous actin (F-actin) to prevent F-actin formation, which blocked activation of the Hippo signaling pathway. In addition, the RNA binding protein Quaking-5 bound directly to hsa_circ_0098181 and induced its biogenesis.ConclusionsOur study reveals changes in circRNA expression from chronic hepatitis, primary HCC, to metastatic HCC. Further, the QKI5-hsa_circ_0098181-eEF2-Hippo signaling pathway exerts a regulatory role in HCC.     

Increased RNA-induced silencing complex (RISC) activity contributes to hepatocellular carcinoma

There is virtually no effective treatment for advanced hepatocellular carcinoma (HCC) and novel targets need to be identified to develop effective treatment. We recently documented that the oncogene Astrocyte elevated gene-1 (AEG-1) plays a seminal role in hepatocarcinogenesis. Employing yeast two-hybrid assay and coimmunoprecipitation followed by mass spectrometry, we identified staphylococcal nuclease domain containing 1 (SND1), a nuclease in the RNA-induced silencing complex (RISC) facilitating RNAi-mediated gene silencing, as an AEG-1 interacting protein. Coimmunoprecipitation and colocalization studies confirmed that AEG-1 is also a component of RISC and both AEG-1 and SND1 are required for optimum RISC activity facilitating small interfering RNA (siRNA) and micro RNA (miRNA)-mediated silencing of luciferase reporter gene. In 109 human HCC samples SND1 was overexpressed in ≈74% cases compared to normal liver. Correspondingly, significantly higher RISC activity was observed in human HCC cells compared to immortal normal hepatocytes. Increased RISC activity, conferred by AEG-1 or SND1, resulted in increased degradation of tumor suppressor messenger RNAs (mRNAs) that are target of oncomiRs. Inhibition of enzymatic activity of SND1 significantly inhibited proliferation of human HCC cells. As a corollary, stable overexpression of SND1 augmented and siRNA-mediated inhibition of SND1 abrogated growth of human HCC cells in vitro and in vivo, thus revealing a potential role of SND1 in hepatocarcinogenesis. CONCLUSION: We unravel a novel mechanism that overexpression of AEG-1 and SND1 leading to increased RISC activity might contribute to hepatocarcinogenesis. Targeted inhibition of SND1 enzymatic activity might be developed as an effective therapy for HCC.     

环状RNA在心血管疾病中的研究现状

随着全基因组分析和RNA测序技术的进步,多种非编码RNA逐渐成为研究热点。环状RNA(circRNA)具有多种细胞功能,其表达的改变与多种病理生理过程及疾病的发生发展相关。circRNA已被证明是心血管疾病方面的重要调节因子,如高血压、动脉粥样硬化、急性心肌梗死、心力衰竭、心脏纤维化等。因此,circRNA有望成为心血管疾病的潜在治疗靶点和生物标志物。在这篇综述中,我们以circRNA的生物学机制为基础,综述了目前有关circRNA作为心血管疾病调节因子和生物标志物的研究进展。     

微小RNA-200家族对糖尿病及其并发症的影响

糖尿病并发症可引起人体心、脑和肾等重要组织和器官损害,严重危害人类健康,但其发病机制并不十分清楚。近年研究发现微小RNA（microRNA,miRNA）在糖尿病及其并发症的发生发展中起重要作用。miRNA是真核生物中一类长度约22～25个核苷酸的内源性非编码小分子RNA,通过转录后机制调控其下游靶基因的表达,进而影响疾病的病理生理学过程。其中miRNA-200（miR-200）家族对糖尿病及其并发症的调控研究较多。miR-200家族不仅对胰岛素相关信号通路具有调控作用,在糖尿病微血管及大血管并发症中也发挥重要调控作用。因此,探讨miR-200家族与糖尿病及其并发症之间的关系,可为糖尿病及其并发症的诊断及治疗提供新的思路。     

Intercellular nanovesicle-mediated microRNA transfer: a mechanism of environmental modulation of hepatocellular cancer cell growth

Hepatocellular carcinoma (HCC) is characterized by a propensity for multifocality, growth by local spread, and dysregulation of multiple signaling pathways. These features may be determined by the tumoral microenvironment. The potential of tumor cells to modulate HCC growth and behavior by secreted proteins has been extensively studied. In contrast, the potential for genetic modulation is poorly understood. We investigated the role and involvement of tumor-derived nanovesicles capable of altering gene expression and characterized their ability to modulate cell signaling and biological effects in other cells. We show that HCC cells can produce nanovesicles and exosomes that differ in both RNA and protein content from their cells of origin. These can be taken up and internalized by other cells and can transmit a functional transgene. The microRNA (miRNA) content of these exosomes was examined, and a subset highly enriched within exosomes was identified. A combinatorial approach to identify potential targets identified transforming growth factor β activated kinase-1 (TAK1) as the most likely candidate pathway that could be modulated by these miRNAs. Loss of TAK1 has been implicated in hepatocarcinogenesis and is a biologically plausible target for intercellular modulation. We show that HCC cell-derived exosomes can modulate TAK1 expression and associated signaling and enhance transformed cell growth in recipient cells. CONCLUSION: Exosome-mediated miRNA transfer is an important mechanism of intercellular communication in HCC cells. These observations identify a unique intercellular mechanism that could potentially contribute to local spread, intrahepatic metastases, or multifocal growth in HCC.