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Towards a universal nomenclature standardization for circular RNAs 实现环状RNA的通用命名标准化
Pub Date : 2020-06-01 DOI: 10.21037/NCRI.2020.03.01
Marina C Costa, F. Enguita
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引用次数: 5
A new hypoxia-responsive lncRNA in metastatic breast cancer 癌症转移中一种新的低氧反应性lncRNA
Pub Date : 2020-06-01 DOI: 10.21037/NCRI.2020.03.03
J. French, S. Edwards
© Non-coding RNA Investigation. All rights reserved. Non-coding RNA Investig 2020;4:5 | http://dx.doi.org/10.21037/ncri.2020.03.03 Metastatic breast cancer, refers to the spread of the disease from the breast to other parts of the body, most often to bone, brain, liver or lungs. Despite advances in breast cancer management, most cancer deaths result from metastases that are resistant to systemic therapies (1). Hypoxia (or reduced oxygen availability) is a hallmark of the breast tumor microenvironment and plays an important role in metastatic progression. Breast tumor cells adapt to hypoxia by increasing the activity of the hypoxiainducible transcription factors (HIF1 and HIF2), which regulate the expression of target genes involved in cancer progression (2). Recent studies have implicated long noncoding RNAs (lncRNAs) in hypoxia/HIF-associated breast cancer metastasis, through various mechanisms. Notable examples include the nuclear lncRNA MALAT1 (metastasis-associated lung adenocarcinoma transcript 1), which is widely reported as a metastasis-promoting lncRNA, however a recent study provided strong evidence that MALAT1 suppresses breast cancer metastasis through inactivation of the TEAD transcription factor (3). HOTAIR (HOX transcript antisense RNA) is highly expressed in primary breast tumors and metastases and associated with poor prognosis. HOTAIR promotes epithelial to mesenchymal transition (EMT) by recruiting the polycomb repressive complex-2 (PRC2) to epigenetically silence target gene promoters (4). Furthermore, hypoxic induction of NEAT1 (nuclear paraspeckle assembly transcript 1) induces the formation of nuclear structures called paraspeckles and retention of F11R (also known as junctional adhesion molecule 1) mRNA in the nucleus (5). Induction of NEAT1 in hypoxia also leads to hallmarks of increased tumorigenesis including acceleration of tumor cell proliferation and inhibition of apoptosis (5). The recent study by Niu et al. (6), provides another example of a hypoxia-responsive lncRNA involved in metastatic breast cancer. The authors initially used RNAseq to identify an hypoxia-inducible antisense lncRNA, called RAB11B-AS1 from MDA-MB-231 breast cancer cells under hypoxic conditions (7). Subsequent ChIP-seq and qPCR showed that HIF2, but not HIF1, was enriched at the RAB11B-AS1 promoter and responsible for hypoxiainduced lncRNA expression. Nui and colleagues then investigated the oncogenic role of RAB11B-AS1 in vitro and in vivo through gainand loss-of function studies. They found ectopic expression of RAB11B-AS1 promoted cell migration and invasion in MDA-MB-231 and SUM159 breast cancer cells, whereas RAB11B-AS1 depletion caused the opposite effect. Orthotopic injection of MDAMB-231 cells, ectopically expressing RAB11B-AS1, into the mammary fat pads of NSG mice, did not affect primary tumor growth, but showed increased expression of the endomucin capillary marker and extensive metastases to the lungs and liver as compared to the con
©非编码RNA调查。版权所有。非编码RNA研究2020;4:5 | http://dx.doi.org/10.21037/ncri.2020.03.03转移性乳腺癌,是指疾病从乳房扩散到身体其他部位,最常见的是骨骼、大脑、肝脏或肺部。尽管乳腺癌治疗取得了进展,但大多数癌症死亡是由于对全身治疗有抵抗力的转移所致(1)。缺氧(或氧气可用性降低)是乳腺肿瘤微环境的一个标志,在转移进展中起着重要作用。乳腺肿瘤细胞通过增加缺氧诱导转录因子(HIF1和HIF2)的活性来适应缺氧,这些转录因子调节参与癌症进展的靶基因的表达(2)。最近的研究表明,长链非编码rna (lncRNAs)通过各种机制参与缺氧/ hif相关的乳腺癌转移。值得注意的例子包括核lncRNA MALAT1(转移相关肺腺癌转录本1),它被广泛报道为促进转移的lncRNA,但最近的一项研究提供了强有力的证据,表明MALAT1通过使TEAD转录因子失活来抑制乳腺癌转移(3)。HOTAIR (HOX转录反义RNA)在原发性乳腺肿瘤和转移中高表达,并与不良预后相关。HOTAIR通过募集多梳抑制复合体-2 (PRC2)从表观遗传上沉默靶基因启动子,促进上皮细胞向间质转化(EMT)(4)。缺氧诱导NEAT1(核旁斑组装转录本1)诱导核旁斑结构的形成和细胞核中F11R(也称为连接粘附分子1)mRNA的保留(5)。缺氧诱导NEAT1也导致肿瘤发生增加的标志,包括肿瘤细胞增殖加速和细胞凋亡抑制(5)。提供了另一个低氧反应lncRNA参与转移性乳腺癌的例子。作者最初使用RNAseq从缺氧条件下的MDA-MB-231乳腺癌细胞中鉴定出一种低氧诱导的反义lncRNA,称为RAB11B-AS1(7)。随后的ChIP-seq和qPCR显示,在RAB11B-AS1启动子处富集HIF2,而不是HIF1,并负责低氧诱导的lncRNA表达。Nui和同事随后通过功能获得和功能丧失研究RAB11B-AS1在体外和体内的致癌作用。他们发现RAB11B-AS1的异位表达促进了MDA-MB-231和SUM159乳腺癌细胞的细胞迁移和侵袭,而RAB11B-AS1的缺失则产生相反的效果。将异位表达RAB11B-AS1的MDAMB-231细胞原位注射到NSG小鼠的乳腺脂肪垫中,不影响原发肿瘤的生长,但与对照组相比,内膜粘液蛋白毛细血管标志物的表达增加,并广泛转移到肺和肝脏。总之,这些结果表明,缺氧诱导的RAB11B-AS1促进乳腺癌细胞向远处组织转移。为了研究RAB11B-AS1促进血管生成的机制,作者分析了缺氧条件下RAB11B-AS1过表达的MDA-MB-231的RNAseq数据。基因本体论分析表明,多种生物过程可能对表型有贡献,尽管很难对结果进行排序,因为编辑评论没有价值
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引用次数: 0
miR-155 modulates fatty acid accumulation by targeting C/EBPβ in free fatty acid-induced steatosis in HepG2 cells miR-155通过靶向C/EBPβ在游离脂肪酸诱导的HepG2细胞脂肪变性中调节脂肪酸积累
Pub Date : 2019-12-03 DOI: 10.21037/NCRI.2019.02.03
Jun Hu, Xiaoming Chen
Background: The pathogenesis of non-alcoholic fatty liver disease (NAFLD) is not well understood, which has led to unsatisfactory therapeutic solutions. In the present study, we investigated the role of miR-155 in free fatty acid (FFA)-exposed HepG2 cells. Furthermore, we determined the target gene of miR-155 involved in intracellular fatty acid accumulation. Methods: HepG2 cells were transfected with miR-155 mimics or inhibitor with or without FFA exposure. miR-155 expression was quantified by quantitative real-time RT-PCR. Intracellular fatty acid accumulation was visualized by Nile red staining, flow cytofluorometric analysis, and fluorescence microscopy. Western blot was used to determine the expression level of the target gene. In addition, functional rescue experiments were performed based on miR-155 inhibitor and siRNAs to the target gene. Results: miR-155 level was significantly elevated in HepG2 cells exposed with FFA. Furthermore, inhibition of miR-155 was observed to promote fatty acid accumulation in the absence of FFA in vitro. In addition, overexpression of miR-155 was capable of blunting fatty acid accumulation in the presence of FFA in vitro. CCAAT/enhancer binding protein β (C/EBPβ) was validated as a target gene of miR-155 involved in fatty acid accumulation. Interfering C/EBPβ in HepG2 cells could reverse the promotion effect of miR-155 inhibitor on lipogenesis. Conclusions: miR-155 controls fatty acid accumulation by targeting C/EBPβ. Intervention of miR-155/C/EBPβ might be a novel therapeutic strategy for NAFLD.
背景:非酒精性脂肪肝(NAFLD)的发病机制尚不清楚,导致治疗方案不理想。在本研究中,我们研究了miR-155在游离脂肪酸(FFA)暴露的HepG2细胞中的作用。此外,我们确定了参与细胞内脂肪酸积累的miR-155的靶基因。方法:用miR-155模拟物或抑制剂转染HepG2细胞,无论是否暴露于FFA。miR-155的表达通过定量实时RT-PCR进行定量。通过尼罗红染色、流式细胞荧光分析和荧光显微镜观察细胞内脂肪酸积累。采用蛋白质印迹法测定靶基因的表达水平。此外,基于miR-155抑制剂和靶基因的siRNA进行了功能拯救实验。结果:FFA暴露于HepG2细胞后,miR-155水平显著升高。此外,在体外没有FFA的情况下,观察到miR-155的抑制促进脂肪酸的积累。此外,在体外存在FFA的情况下,miR-155的过表达能够减缓脂肪酸的积累。CCAAT/增强子结合蛋白β(C/EBPβ)被证实是参与脂肪酸积累的miR-155的靶基因。干扰C/EBPβ在HepG2细胞中的表达可以逆转miR-155抑制剂对脂肪生成的促进作用。结论:miR-155通过靶向C/EBPβ来控制脂肪酸的积累。miR-155/C/EBPβ的干预可能是NAFLD的一种新的治疗策略。
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引用次数: 1
Therapeutic strategies for targeting non-coding RNAs with special emphasis on novel delivery systems 针对非编码rna的治疗策略,特别强调新的递送系统
Pub Date : 2019-12-03 DOI: 10.21037/NCRI.2019.02.02
R. Awasthi, J. Madan, H. Malipeddi, K. Dua, G. Kulkarni
Since, the first report on discovery of double helical structure of DNA by James Watson and Francis Crkk (April 1953, Nature), numerous papers have been published reporting function of non-coding RNAs (ncRNAs). On the basis of evidence and the expert’s opinion, it is well documented that majority of the human genome encodes RNAs that do not code for proteins. The aim of this communication is to summarize the importance of ncRNAs as regulators of several biological and developmental processes. Finally, this laconic review focuses on the approaches investigated for the delivery of ncRNAs.
自James Watson和Francis Crkk首次报道DNA的双螺旋结构(1953年4月,Nature)以来,发表了大量报道非编码RNA(ncRNA)功能的论文。根据证据和专家的意见,有充分的证据表明,大多数人类基因组编码的RNA不编码蛋白质。这篇通讯的目的是总结ncRNA作为几个生物和发育过程的调节因子的重要性。最后,这篇简洁的综述集中在研究ncRNA递送的方法上。
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引用次数: 5
Application of the CARE guideline as reporting standard in the Non-coding RNA Investigation CARE指南作为非编码RNA研究报告标准的应用
Pub Date : 2019-11-01 DOI: 10.21037/ncri.2019.10.03
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引用次数: 0
Regulatory roles of small RNAs in prokaryotes: parallels and contrast with eukaryotic miRNA 小RNA在原核生物中的调节作用:与真核miRNA的相似性和对比
Pub Date : 2019-10-28 DOI: 10.21037/ncri.2019.10.02
Derrick Watkins, D. Arya
Small non-coding RNAs continue to be identified that regulate the processes of translation and transcription in prokaryotes. A variety of regulatory mechanisms have been characterized by these regulatory RNAs that occur by complementary base pairing between the small regulatory RNA (sreRNA) and a target mRNA, including transcription attenuation, translation inhibition, translation activation, and mRNA protection. Here, we discuss the description of these mechanisms, and the key components that contribute to the interactions between the sreRNA and the target mRNA. Additionally, we classify sreRNAs into categories based on their origins. Antisense RNA (asRNA) is defined strictly as cis-encoded, trans-acting regulatory RNA, while small RNA (sRNA) is strictly defined as trans-encoded, trans-acting regulatory RNA. Although both RNAs bind the target mRNA by Watson-Crick base pairing to the complementary sequence of mRNA, sRNA binding typically requires the presence of a chaperone protein, is only partially complementary to the target mRNA, and often targets multiple mRNAs. Therefore, we characterize the mechanism of sRNA as similar to the well characterized eukaryotic miRNA and discuss the parallels and differences between the two. The binding of asRNA to its target mRNA, by contrast, is typically independent of a chaperone protein, is completely or almost completely complementary to the mRNA target sequence and targets only a single mRNA. While this categorization is likely to evolve as the research identifies more relevant and distinguishing characteristics to classify sreRNAs, the classification used here of prokaryotic sreRNAs should lead to a more refined approach to the discussion and investigation of regulatory RNAs until then.
在原核生物中,调节翻译和转录过程的小非编码rna继续被发现。这些调控RNA通过小调控RNA (ssrna)和靶mRNA之间的互补碱基配对发生,包括转录衰减、翻译抑制、翻译激活和mRNA保护,这些调控RNA具有多种调控机制的特征。在这里,我们讨论了这些机制的描述,以及促成sreRNA和目标mRNA之间相互作用的关键成分。此外,我们根据srrna的起源将其分类。反义RNA (asRNA)严格定义为顺式编码、反式作用的调控RNA,而小RNA (sRNA)严格定义为反式编码、反式作用的调控RNA。虽然这两种rna通过沃森-克里克碱基配对与mRNA的互补序列结合靶mRNA,但sRNA结合通常需要伴侣蛋白的存在,仅与靶mRNA部分互补,并且通常靶向多个mRNA。因此,我们将sRNA的机制描述为类似于已被充分表征的真核miRNA,并讨论两者之间的相似之处和差异。相比之下,asRNA与其靶mRNA的结合通常独立于伴侣蛋白,与mRNA靶序列完全或几乎完全互补,并且仅靶向单个mRNA。虽然这种分类可能会随着研究确定更多相关和可区分的特征来分类srerna而发展,但在此之前,原核srerna的分类应该会导致更精细的方法来讨论和研究调控rna。
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引用次数: 7
The exosomes carry new hope for cardiac regeneration 外泌体为心脏再生带来了新希望
Pub Date : 2019-10-17 DOI: 10.21037/ncri.2019.10.01
P. Madeddu
Coronary artery disease (CAD) is the number one cause of death in developed countries (1,2). In the UK alone, there are 2 million people with CAD and 188,000 require treatment for a myocardial infarction (MI) each year. Because of the limited regenerative capacity of the human heart (3), an acute MI causes permanent damage that may ultimately result in heart failure (HF). The management of chronic HF has improved considerably in recent years but, at the same time, healthcare and social costs have rocketed. Therefore, there is an urgent need for new strategies potentially transforming palliative care into curative therapy.
冠状动脉疾病(CAD)是发达国家的头号死因(1,2)。仅在英国,每年就有200万人患有冠心病,18.8万人需要接受心肌梗死(MI)治疗。由于人类心脏的再生能力有限(3),急性心肌梗死会造成永久性损伤,最终可能导致心力衰竭(HF)。近年来,慢性心衰的管理有了很大的改善,但与此同时,医疗保健和社会成本也在飙升。因此,迫切需要有可能将姑息治疗转变为治愈性治疗的新策略。
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引用次数: 0
Non-coding RNAs and drug-induced liver injury 非编码rna与药物性肝损伤
Pub Date : 2019-09-09 DOI: 10.21037/ncri.2019.07.01
Mengxue Sun, Meiyi Song, Fei Wang
Currently, more and more clinical cases of drug-induced liver injury (DILI) are increasing that may lead to acute liver failure and even death. It has been reported that DILI is the main cause of clinical drugs withdrawal, which results in a bad impact on the treatment of many diseases. So far there are still no effective monitoring means and therapeutic approaches for DILI. Nowadays many types of research on non-coding RNAs (ncRNAs), mainly including microRNAs, lncRNAs, and circRNAs, are interesting and have significant effects on lots of diseases, such as diagnostic biomarkers and treatment methods. This article mainly reviews concerning the ncRNAs in DILI to find the new sights of diagnosis and treatments in DILI.
目前,药物性肝损伤(DILI)的临床病例越来越多,可能导致急性肝功能衰竭甚至死亡。据报道,DILI是临床停药的主要原因,给许多疾病的治疗带来了不良影响。到目前为止,DILI还没有有效的监测手段和治疗方法。目前,许多类型的非编码RNA(ncRNA)研究,主要包括微小RNA、lncRNA和circRNA,都很有趣,并对许多疾病产生了重大影响,如诊断生物标志物和治疗方法。本文主要对DILI中的ncRNA进行综述,以期对DILI的诊断和治疗有新的认识。
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引用次数: 0
MiR-20a loaded with nanoparticles helps in the reduction of colorectal liver metastasis 负载纳米颗粒的MiR-20a有助于减少结直肠癌肝转移
Pub Date : 2019-09-01 DOI: 10.21037/NCRI.2018.12.03
Rupal Ojha, V. Prajapati
One of the foremost and worldwide leading cause of death is cancer. The molecular modifications or alterations in the genome leads to the cancerous condition. Many other factors are responsible for the cause of the disease such as lifestyle, age, gender, ecological factors, race, food and heredity (1). Among all the cancers, colorectal cancer is the third most often occurring cancer and responsible for the millions of deaths worldwide.
癌症是世界上最主要的死亡原因之一。基因组中的分子修饰或改变导致癌变。许多其他因素也是导致这种疾病的原因,如生活方式、年龄、性别、生态因素、种族、食物和遗传(1)。在所有癌症中,结直肠癌是第三大最常见的癌症,造成全世界数百万人死亡。
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引用次数: 0
The roles of miRNAs in liver diseases mirna在肝脏疾病中的作用
Pub Date : 2019-08-30 DOI: 10.21037/ncri.2019.08.02
Z. Dai, Taihua Yang, G. Song
Liver, the largest internal organ in vertebrates, plays an essential role in metabolic processes in the body. Many factors, such as viruses and alcohol, can lead to function disorders or even liver failure. Every year more than a million patients suffer from various liver diseases. miRNAs have evolved as important regulators in in liver development, homeostasis, dysfunction, and regeneration. Increasing evidences have shown that miRNAs play an important role in various liver diseases, including acute liver failure (ALF), chronic liver failure as well as liver carcinoma. In this review, we update the roles of miRNAs in liver regeneration, fibrosis and cancer.
肝脏是脊椎动物最大的内脏器官,在人体代谢过程中起着重要作用。许多因素,如病毒和酒精,可导致功能紊乱甚至肝功能衰竭。每年有100多万患者患有各种肝脏疾病。mirna在肝脏发育、体内平衡、功能障碍和再生过程中已成为重要的调节因子。越来越多的证据表明,mirna在多种肝脏疾病中发挥重要作用,包括急性肝衰竭(ALF)、慢性肝衰竭以及肝癌。在这篇综述中,我们更新了mirna在肝脏再生、纤维化和癌症中的作用。
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引用次数: 1
期刊
Non-coding RNA investigation
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