noncoding RNAs

非编码 RNA
  • 文章类型: Journal Article
    外泌体,作为肿瘤微环境中的关键实体,通过不同分子的转移来协调细胞间的通讯,其中非编码RNA(ncRNAs)如miRNA,lncRNAs,和circRNAs起着至关重要的作用。这些ncRNAs,被赋予监管职能,被选择性地掺入到外泌体中。新的证据强调了外泌体ncRNAs在调节甲状腺癌(TC)的关键致癌过程中的重要性,包括扩散,转移,上皮-间质转化(EMT),血管生成,和免疫编辑。外来体的独特组成保护其货物免受酶和化学降解,确保其完整性并促进其在血浆中的特异性表达。这将外泌体ncRNAs定位为TC中新型诊断和预后生物标志物的有希望的候选者。此外,外泌体在TC治疗领域的潜力日益得到认可.这篇综述旨在阐明外泌体ncRNAs与TC之间的复杂关系,培养对他们机械参与的更深入理解。通过这样做,它努力推进对TC中外泌体ncRNAs的探索,最终为基于外泌体及其ncRNA含量的创新诊断和治疗策略铺平道路。
    Exosomes, as pivotal entities within the tumor microenvironment, orchestrate intercellular communication through the transfer of diverse molecules, among which non-coding RNAs (ncRNAs) such as miRNAs, lncRNAs, and circRNAs play a crucial role. These ncRNAs, endowed with regulatory functions, are selectively incorporated into exosomes. Emerging evidence underscores the significance of exosomal ncRNAs in modulating key oncogenic processes in thyroid cancer (TC), including proliferation, metastasis, epithelial-mesenchymal transition (EMT), angiogenesis, and immunoediting. The unique composition of exosomes shields their cargo from enzymatic and chemical degradation, ensuring their integrity and facilitating their specific expression in plasma. This positions exosomal ncRNAs as promising candidates for novel diagnostic and prognostic biomarkers in TC. Moreover, the potential of exosomes in the therapeutic landscape of TC is increasingly recognized. This review aims to elucidate the intricate relationship between exosomal ncRNAs and TC, fostering a deeper comprehension of their mechanistic involvement. By doing so, it endeavors to propel forward the exploration of exosomal ncRNAs in TC, ultimately paving the way for innovative diagnostic and therapeutic strategies predicated on exosomes and their ncRNA content.
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  • 文章类型: Journal Article
    在过去的几十年中,人们对理解表观遗传学在牙周病的发病机理和治疗中的参与越来越感兴趣。非编码RNA(ncRNAs),包括microRNAs(miRNAs),长链非编码RNA(lncRNA),和环状RNAs(circRNAs),可能作为表观遗传修饰因子,影响与炎症和自身免疫性疾病发病机制有关的基因的表达。越来越多的证据支持所有三种类型的ncRNAs的功能似乎是相互依赖的观点。LncRNAs可以充当miRNA诱饵,虽然circRNAs可以充当miRNA海绵,导致miRNA靶基因的再表达。这篇综述的目的是评估ncRNAs在牙周病中的表达模式。研究表明miRNA表达与牙周炎呈正相关;然而,这不能被lncRNAs和circRNAs所宣称,在牙周炎患者中差异表达。一些研究还表明,利用ncRNAs作为牙周炎的诊断和预后生物标志物,甚至作为潜在的治疗靶点;Neving,支持这一点的证据还为时过早。未来精心设计的研究仍然需要建立ncRNAs在牙周病的演变和进展中的功能作用。
    During the last few decades there has been a growing interest in understanding the involvement of epigenetics in the pathogenesis and treatment of periodontal disease. Noncoding RNAs (ncRNAs), including microRNAs (miRNAs), long noncoding RNAs (lncRNAs), and circular RNAs (circRNAs), may serve as epigenetic modifiers affecting the expression of genes involved in the pathogenesis of inflammatory and autoimmune diseases. There is increasing evidence supporting the idea that the function of all three types of ncRNAs seems to be interdependent. LncRNAs can act as miRNA decoys, while circRNAs can act as miRNA sponges, leading to the re-expression of miRNA target genes. The purpose of this review is to evaluate the expression patterns of ncRNAs in periodontal disease. Studies demonstrate a positive correlation between miRNA expression and periodontitis; however, this cannot be claimed for lncRNAs and circRNAs, which appear to be differentially expressed in periodontitis patients. Several studies have also suggested utilizing ncRNAs as diagnostic and prognostic biomarkers in periodontitis, or even as potential therapeutic targets; Nevetheless, the evidence to support this is premature. Future well-designed research remains necessary to establish the functional role of ncRNAs in the evolution and progression of periodontal disease.
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  • 文章类型: Journal Article
    我们之前的研究确定了与糖尿病终末期肾病(ESKD)进展相关的8种风险和9种保护性血浆miRNA。本研究旨在阐明影响循环miRNA定量的分析前因素。使用EdgeSeq平台,定量血浆中的2,002个miRNA,包括ESKD相关的miRNA,我们比较了整个血浆中的miRNA谱与从相同血浆标本中提取的RNA中的miRNA谱.在从血浆中提取的标准RNA中检测到少于一半的miRNA。与EdgeSeq相比,当通过RNA测序(RNA-Seq)或定量逆转录PCR(qRT-PCR)平台定量从血浆提取的RNA时,个体和miRNA的浓度的检测低得多。通过EdgeSeq平台确定的miRNA的血浆谱在评估中具有极好的可重复性,并且随着年龄的增长没有变化。性别,血红蛋白A1c,BMI,和冷冻储存时间。仅在整个血浆中并使用EdgeSeq平台准确检测和测量风险ESKD相关miRNA。除qRT-PCR外,所有平台均可检测到保护性ESKD相关miRNA;然而,用不同平台获得的浓度之间的相关性较弱或不存在。总之,分析前因素对糖尿病ESKD中循环miRNA的检测和定量具有深远的影响。定量整个血浆中的miRNA并使用EdgeSeq平台可能是研究与ESKD和可能的其他疾病相关的循环无细胞miRNA谱的优选方法。
    Our previous study identified 8 risk and 9 protective plasma miRNAs associated with progression to end-stage kidney disease (ESKD) in diabetes. This study aimed to elucidate preanalytical factors that influence the quantification of circulating miRNAs. Using the EdgeSeq platform, which quantifies 2,002 miRNAs in plasma, including ESKD-associated miRNAs, we compared miRNA profiles in whole plasma versus miRNA profiles in RNA extracted from the same plasma specimens. Less than half of the miRNAs were detected in standard RNA extraction from plasma. Detection of individual and concentrations of miRNAs were much lower when RNA extracted from plasma was quantified by RNA sequencing (RNA-Seq) or quantitative reverse transcription PCR (qRT-PCR) platforms compared with EdgeSeq. Plasma profiles of miRNAs determined by the EdgeSeq platform had excellent reproducibility in assessment and had no variation with age, sex, hemoglobin A1c, BMI, and cryostorage time. The risk ESKD-associated miRNAs were detected and measured accurately only in whole plasma and using the EdgeSeq platform. Protective ESKD-associated miRNAs were detected by all platforms except qRT-PCR; however, correlations among concentrations obtained with different platforms were weak or nonexistent. In conclusion, preanalytical factors have a profound effect on detection and quantification of circulating miRNAs in ESKD in diabetes. Quantification of miRNAs in whole plasma and using the EdgeSeq platform may be the preferable method to study profiles of circulating cell-free miRNAs associated with ESKD and possibly other diseases.
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  • 文章类型: Editorial
    RNA生物学彻底改变了对癌症的理解和治疗,尤其是内分泌相关恶性肿瘤。这篇社论强调了RNA在癌症进展中的关键作用,强调其对肿瘤异质性和行为的影响。选择性剪接和非编码RNA调控等过程塑造了癌症生物学,与microRNA,长链非编码RNA,和环状RNA协调基因表达动力学。异常RNA特征有望作为内分泌相关癌症的诊断和预后生物标志物。最近的发现,如异常的PI3Kδ剪接亚型和上皮-间质转化相关的lncRNA特征,揭示个性化治疗的潜在治疗目标。对m6A相关lncRNA预后模型和lncRNALINC00659在胃癌中的功能的见解代表了该领域正在进行的研究。随着对RNA在癌症中的作用的理解的扩展,个性化治疗在管理内分泌相关恶性肿瘤方面提供了转化潜力.这标志着精确肿瘤学的重大进步,促进更有效的癌症治疗创新。
    RNA biology has revolutionized cancer understanding and treatment, especially in endocrine-related malignancies. This editorial highlights RNA\'s crucial role in cancer progression, emphasizing its influence on tumor heterogeneity and behavior. Processes like alternative splicing and noncoding RNA regulation shape cancer biology, with microRNAs, long noncoding RNAs, and circular RNAs orchestrating gene expression dynamics. Aberrant RNA signatures hold promise as diagnostic and prognostic biomarkers in endocrine-related cancers. Recent findings, such as aberrant PI3Kδ splice isoforms and epithelial-mesenchymal transition-related lncRNA signatures, unveil potential therapeutic targets for personalized treatments. Insights into m6A-associated lncRNA prognostic models and the function of lncRNA LINC00659 in gastric cancer represents ongoing research in this field. As understanding of RNA\'s role in cancer expands, personalized therapies offer transformative potential in managing endocrine-related malignancies. This signifies a significant stride towards precision oncology, fostering innovation for more effective cancer care.
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  • 文章类型: Journal Article
    昆虫通过分泌抗菌肽(AMPs)和通过NF-κB转录因子的免疫效应因子来依赖针对入侵者的体液免疫,肠道细菌菌群改善了它们的适应性。尽管有越来越多的非编码RNA(ncRNA)参与针对病原体的免疫应答的报道,Riptortuspedestris中ncRNA-AMP调控网络的综合研究,这是东亚广泛分布的害虫之一,在喂养环境变化的情况下,仍然没有得到很好的理解。这项研究的目的是采用全转录组测序(WTS)来系统地鉴定lncRNAs(长链非编码RNA)和circRNAs(环状RNA),并在不同的喂养条件下获得它们从牛腹中的差异表达。功能注释表明,它们主要富集在GO和KEGG数据库的各种生物过程中,尤其是在免疫信号通路中。从WTS数据中鉴定并表征了5个防御素(4个新成员)和11个溶菌酶(9个新成员)家族基因,同时,系统发育分析证实了它们的分类。随后,基于生物信息学预测和计算,预测并建立了上述两种AMPs的miRNA-mRNA相互作用网络和一种溶菌酶的lncRNA参与的ceRNA(竞争性内源性RNA)调控网络,和差异表达(DE)防御素的表达模式,在所有比较组中估计和选择DE溶菌酶和相关的DEncRNAs。最后,整合WTS和之前的16SrRNA扩增子测序的分析,我们进行了Pearson相关性分析,以揭示上述DEAMP和ncRNAs之间的显著正相关或负相关,以及R.pedestris属水平的肠道细菌菌群的大多数变化。一起来看,当前的观察结果为响应昆虫饲养环境变化的AMP的ncRNA调控网络提供了很好的见解,并揭示了未来害虫防治的新潜在策略。
    Insects depend on humoral immunity against intruders through the secretion of antimicrobial peptides (AMPs) and immune effectors via NF-κB transcription factors, and their fitness is improved by gut bacterial microbiota. Although there are growing numbers of reports on noncoding RNAs (ncRNAs) involving in immune responses against pathogens, comprehensive studies of ncRNA-AMP regulatory networks in Riptortus pedestris, which is one of the widely distributed pests in East Asia, are still not well understood under feeding environmental changes. The objective of this study employed the whole-transcriptome sequencing (WTS) to systematically identify the lncRNAs (long noncoding RNA) and circRNAs (circular RNA) and to obtain their differential expression from the R. pedestris gut under different feeding conditions. Functional annotation indicated that they were mainly enriched in various biological processes with the GO and KEGG databases, especially in immune signaling pathways. Five defensin (four novel members) and eleven lysozyme (nine novel members) family genes were identified and characterized from WTS data, and meanwhile, phylogenetic analysis confirmed their classification. Subsequently, the miRNA-mRNA interaction network of above two AMPs and lncRNA-involved ceRNA (competing endogenous RNA) regulatory network of one lysozyme were predicted and built based on bioinformatic prediction and calculation, and the expression patterns of differentially expressed (DE) defensins, and DE lysozymes and related DE ncRNAs were estimated and selected among all the comparison groups. Finally, to integrate the analyses of WTS and previous 16S rRNA amplicon sequencing, we conducted the Pearson correlation analysis to reveal the significantly positive or negative correlation between above DE AMPs and ncRNAs, as well as most changes in the gut bacterial microbiota at the genus level of R. pedestris. Taken together, the present observations provide great insights into the ncRNA regulatory networks of AMPs in response to rearing environmental changes in insects and uncover new potential strategies for pest control in the future.
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  • 文章类型: Journal Article
    肝细胞癌(HCC)是最常见的原发性肝脏恶性肿瘤,由于患病率的增加,其发病率在全球范围内也在增加。代谢重编程已被认为是癌症的标志,并在癌症进展中起作用。葡萄糖,脂质和氨基酸是三种主要成分,它们的代谢改变可以直接影响细胞的能量产生,包括肝癌细胞.营养和能量对于癌细胞的生长和增殖是不可或缺的,因此改变肝癌细胞的代谢可以抑制肝癌的进展。本综述总结了最近对肿瘤调节分子的研究,包括许多非编码RNA,癌基因和肿瘤抑制基因,调节葡萄糖的代谢活动,通过靶向关键酶的脂质和氨基酸,信号通路或两者之间的相互作用。这些调节分子可以调节癌细胞的快速增殖,肿瘤进展和治疗抵抗。据认为,这些肿瘤调节因子可作为肝癌的治疗靶点或有价值的生物标志物。具有减轻HCC耐药性的潜力。此外,代谢抑制剂作为肝癌治疗方法的优缺点,以及可能的解决方案进行了讨论,为开发更有效的HCC治疗策略提供见解。
    Hepatocellular carcinoma (HCC) is the most common primary liver malignancy and its morbidity is increasing worldwide due to increasing prevalence. Metabolic reprogramming has been recognized as a hallmark of cancer and serves a role in cancer progression. Glucose, lipids and amino acids are three major components whose altered metabolism can directly affect the energy production of cells, including liver cancer cells. Nutrients and energy are indispensable for the growth and proliferation of cancer cells, thus altering the metabolism of hepatoma cells can inhibit the progression of HCC. The present review summarizes recent studies on tumour regulatory molecules, including numerous noncoding RNAs, oncogenes and tumour suppressors, which regulate the metabolic activities of glucose, lipids and amino acids by targeting key enzymes, signalling pathways or interactions between the two. These regulatory molecules can regulate the rapid proliferation of cancer cells, tumour progression and treatment resistance. It is thought that these tumour regulatory factors may serve as therapeutic targets or valuable biomarkers for HCC, with the potential to mitigate HCC drug resistance. Furthermore, the advantages and disadvantages of metabolic inhibitors as a treatment approach for HCC, as well as possible solutions are discussed, providing insights for developing more effective treatment strategies for HCC.
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  • 文章类型: Journal Article
    通过表观遗传机制理解基因表达调控的进展有助于阐明非编码RNA作为几种疾病的药理靶标的调控机制。microRNAs(miRs)是一类进化保守的,短,非编码RNA通过靶向mRNA3'-非翻译区的特定序列在转录后水平上以协调的方式调节基因表达。相反,心血管疾病(CVD)的机制由于其生命过程的起源而在很大程度上仍然难以捉摸,多因素病理生理学,和合并症。在这方面,由于对单一疗法的进行性抵抗,使用常规药物进行CVD治疗会导致治疗失败。忽略了所涉及的多种因素,并降低对多药理学方法的依从性。因此,考虑到它在调节完整基因通路中的作用,基于miR的药物已明显进展到临床前和临床试验。这篇综述总结了目前关于miR在心血管疾病中的作用机制的知识。重点是描述临床化学和物理学如何提高miR分子的稳定性。此外,提供了与心血管疾病有关的主要miRs以及将这些分子用作活性药理分子的临床试验的全面综述.
    Advances in understanding gene expression regulation through epigenetic mechanisms have contributed to elucidating the regulatory mechanisms of noncoding RNAs as pharmacological targets in several diseases. MicroRNAs (miRs) are a class of evolutionarily conserved, short, noncoding RNAs regulating in a concerted manner gene expression at the post-transcriptional level by targeting specific sequences of the 3\'-untranslated region of mRNA. Conversely, mechanisms of cardiovascular disease (CVD) remain largely elusive due to their life-course origins, multifactorial pathophysiology, and co-morbidities. In this regard, CVD treatment with conventional medications results in therapeutic failure due to progressive resistance to monotherapy, which overlooks the multiple factors involved, and reduced adherence to poly-pharmacology approaches. Consequently, considering its role in regulating complete gene pathways, miR-based drugs have appreciably progressed into preclinical and clinical testing. This review summarizes the current knowledge about the mechanisms of miRs in cardiovascular disease, focusing specifically on describing how clinical chemistry and physics have improved the stability of the miR molecule. In addition, a comprehensive review of the main miRs involved in cardiovascular disease and the clinical trials in which these molecules are used as active pharmacological molecules is provided.
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  • 文章类型: Journal Article
    非编码RNA(ncRNAs)在重要通路的调控中发挥关键作用,包括细胞生长,压力管理,信令,和生物膜的形成。硫酸盐还原细菌(SRB)造成巨大的经济损失,导致微生物通过金属表面的生物膜引起腐蚀。为了有效应对SRB带来的挑战,了解它们形成生物膜的分子机制至关重要。本研究旨在鉴定模型SRB基因组中的ncRNAs,阿拉斯加油磺弧菌G20(OAG20)。三种计算机模拟方法揭示了在OAG20中不包括tRNA的37个ncRNA的全基因组分布。这些ncRNAs属于18个不同的Rfam家族。这项研究确定了核糖开关,sRNAs,RNP,SRP。分析表明,这些ncRNAs可能在OAG20生物膜形成中涉及的几种生物合成和运输途径的调节中起关键作用。三个sRNAs,假单胞菌P10,II型锤头,在OAG20中发现的sX4很少见,它们的作用在SRB中尚未确定。这些结果表明,应用各种计算方法可以丰富结果,并导致发现其他新的ncRNAs。这可能会导致理解生物膜形成过程中的“OAG20的生命规则”。
    Noncoding RNAs (ncRNAs) play key roles in the regulation of important pathways, including cellular growth, stress management, signaling, and biofilm formation. Sulfate-reducing bacteria (SRB) contribute to huge economic losses causing microbial-induced corrosion through biofilms on metal surfaces. To effectively combat the challenges posed by SRB, it is essential to understand their molecular mechanisms of biofilm formation. This study aimed to identify ncRNAs in the genome of a model SRB, Oleidesulfovibrio alaskensis G20 (OA G20). Three in silico approaches revealed genome-wide distribution of 37 ncRNAs excluding tRNAs in the OA G20. These ncRNAs belonged to 18 different Rfam families. This study identified riboswitches, sRNAs, RNP, and SRP. The analysis revealed that these ncRNAs could play key roles in the regulation of several pathways of biosynthesis and transport involved in biofilm formation by OA G20. Three sRNAs, Pseudomonas P10, Hammerhead type II, and sX4, which were found in OA G20, are rare and their roles have not been determined in SRB. These results suggest that applying various computational methods could enrich the results and lead to the discovery of additional novel ncRNAs, which could lead to understanding the \"rules of life of OA G20\" during biofilm formation.
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  • 文章类型: Journal Article
    表观遗传机制是细胞正常发育的基石,协调哺乳动物细胞中的组织特异性基因表达。在这个复杂的景观畸变驱动基因功能的实质性变化,成为癌症病因和进展的关键。虽然癌症通常被认为是一种遗传性疾病,其当代定义包括与破坏性表观遗传异常交织在一起的遗传改变。这篇综述探讨了DNA甲基化的深刻影响,组蛋白修饰,和基本细胞过程中的非编码RNA。当这些关键的表观遗传机制受到破坏时,它们错综复杂地引导着在看似正常的细胞中获得癌症的6个标志特征。利用解码这些表观遗传复杂性的最新进展带来了巨大的希望,预示着在开发针对由异常表观遗传修饰驱动的癌症的靶向和更有效的治疗方式方面的新时代。
    Epigenetic machinery is a cornerstone in normal cell development, orchestrating tissue-specific gene expression in mammalian cells. Aberrations in this intricate landscape drive substantial changes in gene function, emerging as a linchpin in cancer etiology and progression. While cancer was conventionally perceived as solely a genetic disorder, its contemporary definition encompasses genetic alterations intertwined with disruptive epigenetic abnormalities. This review explores the profound impact of DNA methylation, histone modifications, and noncoding RNAs on fundamental cellular processes. When these pivotal epigenetic mechanisms undergo disruption, they intricately guide the acquisition of the 6 hallmark characteristics of cancer within seemingly normal cells. Leveraging the latest advancements in decoding these epigenetic intricacies holds immense promise, heralding a new era in developing targeted and more efficacious treatment modalities against cancers driven by aberrant epigenetic modifications.
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  • 文章类型: Journal Article
    胰腺β细胞的丢失或功能障碍,负责胰岛素分泌,构成了所有形式的糖尿病的基础,全世界广泛流行的疾病。用源自干细胞的再生或移植细胞替代受损的β细胞是一种有前途的治疗策略。然而,在体外诱导干细胞分化为功能齐全的葡萄糖反应β细胞已被证明是具有挑战性的。非编码RNA(ncRNAs)已经成为控制分化的关键调节因子,身份,和β细胞的功能。此外,工程水凝胶系统,生物材料,和器官样结构具有可提供支持干细胞分化的三维(3D)微环境的工程特性。这篇综述总结了ncRNAs在维持分化中的作用和贡献,身份,和β细胞的功能。它专注于调节干细胞中ncRNAs的水平,以激活β细胞遗传程序来产生替代β细胞,并讨论如何通过结合水凝胶系统和其他组织工程材料来操纵ncRNA表达。阐明β细胞生物学中ncRNA介导的调节模式并利用这些知识控制干细胞分化可能为糖尿病细胞替代疗法和组织工程中产生功能性胰岛素产生细胞提供有希望的治疗策略。
    The loss or dysfunction of pancreatic β-cells, which are responsible for insulin secretion, constitutes the foundation of all forms of diabetes, a widely prevalent disease worldwide. The replacement of damaged β-cells with regenerated or transplanted cells derived from stem cells is a promising therapeutic strategy. However, inducing the differentiation of stem cells into fully functional glucose-responsive β-cells in vitro has proven to be challenging. Noncoding RNAs (ncRNAs) have emerged as critical regulatory factors governing the differentiation, identity, and function of β-cells. Furthermore, engineered hydrogel systems, biomaterials, and organ-like structures possess engineering characteristics that can provide a three-dimensional (3D) microenvironment that supports stem cell differentiation. This review summarizes the roles and contributions of ncRNAs in maintaining the differentiation, identity, and function of β-cells. And it focuses on regulating the levels of ncRNAs in stem cells to activate β-cell genetic programs for generating alternative β-cells and discusses how to manipulate ncRNA expression by combining hydrogel systems and other tissue engineering materials. Elucidating the patterns of ncRNA-mediated regulation in β-cell biology and utilizing this knowledge to control stem cell differentiation may offer promising therapeutic strategies for generating functional insulin-producing cells in diabetes cell replacement therapy and tissue engineering.
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