Non-coding RNAs

非编码 RNA
  • 文章类型: Journal Article
    前列腺癌(PCa)在实体瘤中诊断频率最高,是癌症相关死亡的主要原因。非编码RNA(ncRNAs),比如microRNA,长链非编码RNA和环状RNA,经常表现出失调并显著影响PCa的生物学行为。与循环ncRNAs相比,由于脂双层的保护作用,加载到外泌体中的ncRNA更稳定。此外,外泌体ncRNAs促进分子和信息的细胞间转移。越来越多的证据表明,外泌体ncRNAs在进展中具有有希望的潜力,PCa的诊断和预后。这篇综述旨在讨论外泌体ncRNAs在PCa中的功能。评估其作为临床生物标志物和治疗靶标的可能应用,并提供PCa中ncRNAs调控网络的全面概述。我们还鉴定了可以用作诊断生物标志物的ncRNAs,分期,PCa的分级和预后评估。这篇综述为研究人员提供了一个关于PCa外泌体ncRNAs功能的新观点,并为其诊断提供了额外的选择。进展监测,和预后预测。
    Prostate cancer (PCa) has the highest frequency of diagnosis among solid tumors and ranks second as the primary cause of cancer-related deaths. Non-coding RNAs (ncRNAs), such as microRNAs, long non-coding RNAs and circular RNAs, frequently exhibit dysregulation and substantially impact the biological behavior of PCa. Compared with circulating ncRNAs, ncRNAs loaded into exosomes are more stable because of protection by the lipid bilayer. Furthermore, exosomal ncRNAs facilitate the intercellular transfer of molecules and information. Increasing evidence suggests that exosomal ncRNAs hold promising potential in the progression, diagnosis and prognosis of PCa. This review aims to discuss the functions of exosomal ncRNAs in PCa, evaluate their possible applications as clinical biomarkers and therapeutic targets, and provide a comprehensive overview of the ncRNAs regulatory network in PCa. We also identified ncRNAs that can be utilized as biomarkers for diagnosis, staging, grading and prognosis assessment in PCa. This review offers researchers a fresh perspective on the functions of exosomal ncRNAs in PCa and provides additional options for its diagnosis, progression monitoring, and prognostic prediction.
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  • 文章类型: Journal Article
    耐药性影响了化疗的疗效。包括P-糖蛋白(P-gp)在内的药物转运蛋白的失调可以通过药物外排介导耐药性。在这次审查中,我们强调了P-gp在肿瘤耐药中的作用以及相关的分子通路,包括磷酸肌醇3-激酶(PI3K)-Akt,磷酸酶和张力蛋白同源物(PTEN)和核因子-κB(NF-κB),以及非编码RNA(ncRNAs)。细胞分泌的胞外囊泡可以转运ncRNAs和其他蛋白,从而改变肿瘤耐药中的P-gp活性。P-gp需要ATP才能发挥作用,线粒体功能障碍的诱导或谷氨酰胺代谢的抑制可以损害P-gp功能,从而增加化学敏感性。植物化学品,小分子和纳米颗粒已被引入作为P-gp抑制剂,以提高人类癌症的药物敏感性。
    Drug resistance has compromised the efficacy of chemotherapy. The dysregulation of drug transporters including P-glycoprotein (P-gp) can mediate drug resistance through drug efflux. In this review, we highlight the role of P-gp in cancer drug resistance and the related molecular pathways, including phosphoinositide 3-kinase (PI3K)-Akt, phosphatase and tensin homolog (PTEN) and nuclear factor-κB (NF-κB), along with non-coding RNAs (ncRNAs). Extracellular vesicles secreted by the cells can transport ncRNAs and other proteins to change P-gp activity in cancer drug resistance. P-gp requires ATP to function, and the induction of mitochondrial dysfunction or inhibition of glutamine metabolism can impair P-gp function, thus increasing chemosensitivity. Phytochemicals, small molecules and nanoparticles have been introduced as P-gp inhibitors to increase drug sensitivity in human cancers.
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  • 文章类型: Journal Article
    肝癌是一个全球性的健康挑战,造成重大的社会经济负担。肝细胞癌(HCC)是原发性肝癌的主要类型,在分子和细胞特征方面是高度异质的。早期或小肿瘤通常用手术或消融治疗。目前,化疗和免疫疗法是不可切除肿瘤或晚期HCC的最佳治疗方法。然而,药物反应和获得性耐药是不可预测的与现有的系统指南有关的突变模式和分子生物标志物,导致许多非典型分子谱患者的治疗结局不佳。凭借先进的技术平台,有价值的信息,如肿瘤遗传改变,表观遗传数据,和肿瘤微环境可以从液体活检获得。说明了肝癌的肿瘤间和肿瘤内异质性,这些数据为治疗方案的决策过程提供了坚实的证据.本文回顾了目前对HCC检测方法的理解,旨在更新使用液体活检进行HCC监测的发展。最近在分子基础上的重要发现,表观遗传概况,循环肿瘤细胞,循环DNA,和组学研究详细阐述了肝癌的诊断。此外,讨论了与治疗选择相关的生物标志物。还强调了一些最近关于靶向治疗的值得注意的临床试验。提供见解,将知识转化为潜在的生物标志物,用于检测和诊断。预后,治疗反应,以及在临床实践中的耐药指标。
    Liver cancer is a global health challenge, causing a significant social-economic burden. Hepatocellular carcinoma (HCC) is the predominant type of primary liver cancer, which is highly heterogeneous in terms of molecular and cellular signatures. Early-stage or small tumors are typically treated with surgery or ablation. Currently, chemotherapies and immunotherapies are the best treatments for unresectable tumors or advanced HCC. However, drug response and acquired resistance are not predictable with the existing systematic guidelines regarding mutation patterns and molecular biomarkers, resulting in sub-optimal treatment outcomes for many patients with atypical molecular profiles. With advanced technological platforms, valuable information such as tumor genetic alterations, epigenetic data, and tumor microenvironments can be obtained from liquid biopsy. The inter- and intra-tumoral heterogeneity of HCC are illustrated, and these collective data provide solid evidence in the decision-making process of treatment regimens. This article reviews the current understanding of HCC detection methods and aims to update the development of HCC surveillance using liquid biopsy. Recent critical findings on the molecular basis, epigenetic profiles, circulating tumor cells, circulating DNAs, and omics studies are elaborated for HCC diagnosis. Besides, biomarkers related to the choice of therapeutic options are discussed. Some notable recent clinical trials working on targeted therapies are also highlighted. Insights are provided to translate the knowledge into potential biomarkers for detection and diagnosis, prognosis, treatment response, and drug resistance indicators in clinical practice.
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  • 文章类型: Journal Article
    在过去的十年里,由RNAPolII产生的调节性非编码RNA(ncRNA)已被揭示为各种基本细胞功能中的有意义的参与者。特别是,成千上万的ncRNAs产生在转录调控元件,如增强子和启动子,它们可以发挥多种功能来规范适当的发展,细胞编程,转录或基因组稳定性。这里,我们回顾了涉及这些调控元件相关ncRNAs的机制,特别是增强子RNA(eRNA)和PROMoteruPstream转录本(PROMPT)。我们将这些短寿命RNA的加工和降解所描述的机制情境化。我们总结了最近的发现,解释了ncRNAs如何在启动子和增强子上局部运作。或者更远的地方,在它们被RNAPolII产生后不久,或通过转录后稳定。这样的发现导致了一个融合模型,解释了ncRNAs如何影响细胞命运,通过作用于转录和染色质结构,这可能进一步涉及参与3D核组织的因素。
    Over the past decade, regulatory non-coding RNAs (ncRNAs) produced by RNA Pol II have been revealed as meaningful players in various essential cellular functions. In particular, thousands of ncRNAs are produced at transcriptional regulatory elements such as enhancers and promoters, where they may exert multiple functions to regulate proper development, cellular programming, transcription or genomic stability. Here, we review the mechanisms involving these regulatory element-associated ncRNAs, and particularly enhancer RNAs (eRNAs) and PROMoter uPstream Transcripts (PROMPTs). We contextualize the mechanisms described to the processing and degradation of these short lived RNAs. We summarize recent findings explaining how ncRNAs operate locally at promoters and enhancers, or further away, either shortly after their production by RNA Pol II, or through post-transcriptional stabilization. Such discoveries lead to a converging model accounting for how ncRNAs influence cellular fate, by acting on transcription and chromatin structure, which may further involve factors participating to 3D nuclear organization.
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  • 文章类型: Journal Article
    腹膜转移(PM)的病理生理学是复杂的,尚未完全了解。PM,起源于胃肠道(GI)癌症,由于其复杂的性质和有限的治疗选择,是一种显著恶化患者预后的疾病。非编码RNA(ncRNAs)已被证明在癌症生物学中起关键作用,影响肿瘤发生,programming,转移,和治疗抗性。越来越多的证据证明了不同类型ncRNAs的调节功能,包括PM中的microRNAs(miRNAs)和长链非编码RNAs(lncRNAs)。识别用于早期检测PM的生物标志物是改善患者预后的关键一步。以及ncRNA谱与生存率的关系,对治疗的反应,和复发风险近年来备受关注。此外,探索利用ncRNAs的创新治疗方法,如靶向治疗和基因沉默,可能会为治疗这种可怕的疾病提供新的视野。系统治疗的最新进展和新型局部区域疗法的发展为多模式治疗方法打开了大门。根治性手术联合腹腔热化疗(HIPEC)已显示出有希望的结果,延长患者生存期。目前的研究主要集中在PM的分子表征,这对于早期发现和制定未来的治疗策略至关重要。通过总结最新发现,这项研究强调了ncRNAs在增强诊断中的转化潜力,预后,和PM在胃肠道癌症中的治疗,为更个性化和有效的临床策略铺平道路。
    Peritoneal metastasis (PM) pathophysiology is complex and not fully understood. PM, originating from gastrointestinal (GI) cancer, is a condition that significantly worsens patient prognosis due to its complex nature and limited treatment options. The non-coding RNAs (ncRNAs) have been shown to play pivotal roles in cancer biology, influencing tumorigenesis, progression, metastasis, and therapeutic resistance. Increasing evidence has demonstrated the regulatory functions of different classes of ncRNAs, including microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) in PM. Identifying biomarkers for early detection of PM is a crucial step towards improving patient outcomes, and how ncRNA profiles correlate with survival rates, response to therapy, and recurrence risks have raised much attention in recent years. Additionally, exploring innovative therapeutic approaches utilizing ncRNAs, such as targeted therapy and gene silencing, may offer new horizons in treating this dire condition. Recent advances in systemic treatments and the development of novel loco-regional therapies have opened doors to multimodal treatment approaches. Radical surgeries combined with hyperthermic intraperitoneal chemotherapy (HIPEC) have shown promising results, leading to extended patient survival. Current research is focused on the molecular characterization of PM, which is crucial for early detection and developing future therapeutic strategies. By summarizing the latest findings, this study underscores the transformative potential of ncRNAs in enhancing the diagnosis, prognosis, and treatment of PM in GI cancer, paving the way for more personalized and effective clinical strategies.
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  • 文章类型: Journal Article
    炎症和自身免疫性疾病(AD)是免疫系统过度活跃的常见结果。炎症是由于免疫系统对破坏性刺激的反应而发生的。外泌体被认为是解决过度活跃的免疫系统的一种先进的治疗方法。将它们定位为治疗AD的有希望的选择。间充质干细胞(MSCs)释放具有强免疫调节作用的外泌体,受它们起源细胞的影响。MSCs-外泌体,作为一种无细胞疗法,与基于细胞的疗法相比,表现出较低的毒性并引起减弱的免疫反应。外来体非编码RNA(ncRNA),特别是microRNAs(miRNAs)和长链非编码RNAs(lncRNAs)与人类健康的各种生物学和功能方面错综复杂。外泌体ncRNAs可以导致组织功能障碍,老化,以及由于各种内部或外部问题而导致的组织特异性改变的疾病。在这项研究中,我们将研究当前外泌体ncRNA关于AD的研究趋势。然后,将概述MSC-外泌体ncRNA的治疗用途,粒子专注于潜在的分子机制。
    Inflammation and autoimmune diseases (AD) are common outcomes of an overactive immune system. Inflammation occurs due to the immune system reacting to damaging stimuli. Exosomes are being recognized as an advanced therapeutic approach for addressing an overactive immune system, positioning them as a promising option for treating AD. Mesenchymal stem cells (MSCs) release exosomes that have strong immunomodulatory effects, influenced by their cell of origin. MSCs-exosomes, being a cell-free therapy, exhibit less toxicity and provoke a diminished immune response compared to cell-based therapies. Exosomal non-coding RNAs (ncRNA), particularly microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) are intricately linked to various biological and functional aspects of human health. Exosomal ncRNAs can lead to tissue malfunction, aging, and illnesses when they experience tissue-specific alterations as a result of various internal or external problems. In this study, we will examine current trends in exosomal ncRNA researches regarding AD. Then, therapeutic uses of MSCs-exosomal ncRNA will be outlined, with a particle focus on the underlying molecular mechanisms.
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  • 文章类型: Journal Article
    癌症相关死亡的主要原因是癌症转移到其他身体部位,糖酵解的增加对于癌细胞维持其高水平的生长和能量需求至关重要,最终促进肿瘤的侵袭和扩散。Warburg效应在癌症的发展中起着重要作用,专注于抑制有氧糖酵解可以为抗癌治疗提供有希望的策略。各种糖酵解过程与肿瘤转移有关,主要涉及非编码RNA(ncRNAs),信号通路,转录因子,还有更多.各种类别的非编码RNA,包括microRNAs(miRNAs),长链非编码RNA(lncRNA),和环状RNAs(circRNAs),在影响与肿瘤扩散相关的葡萄糖代谢方面表现出了希望。此外,环状RNA(circRNAs)和长链非编码RNA(lncRNAs)主要通过螯合microRNAs作为竞争性内源性RNA(ceRNAs),从而调节靶基因的表达并对癌细胞的代谢过程产生重大影响。此外,通过糖酵解的肿瘤转移过程还包括各种信号通路(如PI3K/AKT,HIF,Wnt/β-连环蛋白,和ERK,其中)和转录因子。本文描述了非编码RNA的主要机制,信号通路,和转录因子有助于肿瘤转移的糖酵解。它还研究了这些因素作为癌症治疗的预后标志物和靶标的潜在用途。该手稿还探讨了特定中药和临床西药在通过糖酵解机制抑制肿瘤扩散方面的创新应用,作为抗癌药物的新候选人提供潜力。
    The main cause of cancer-related fatalities is cancer metastasis to other body parts, and increased glycolysis is crucial for cancer cells to maintain their elevated levels of growth and energy requirements, ultimately facilitating the invasion and spread of tumors. The Warburg effect plays a significant role in the advancement of cancer, and focusing on the suppression of aerobic glycolysis could offer a promising strategy for anti-cancer treatment. Various glycolysis processes are associated with tumor metastasis, primarily involving non-coding RNA (ncRNAs), signaling pathways, transcription factors, and more. Various categories of noncoding RNAs, including microRNAs (miRNAs), long noncoding RNAs (lncRNAs), and circular RNAs (circRNAs), have shown promise in influencing glucose metabolism associated with the spread of tumors. Additionally, circular RNAs (circRNAs) and long non-coding RNAs (lncRNAs) predominantly act as competitive endogenous RNAs (ceRNAs) by sequestering microRNAs, thereby modulating the expression of target genes and exerting significant influence on the metabolic processes of cancerous cells. Furthermore, the process of tumor metastasis through glycolysis also encompasses various signaling pathways (such as PI3K/AKT, HIF, Wnt/β- Catenin, and ERK, among others) and transcription factors. This article delineates the primary mechanisms through which non-coding RNAs, signaling pathways, and transcription factors contribute to glycolysis in tumor metastasis. It also investigates the potential use of these factors as prognostic markers and targets for cancer treatment. The manuscript also explores the innovative applications of specific traditional Chinese medicine and clinical Western medications in inhibiting tumor spread through glycolysis mechanisms, offering potential as new candidates for anti-cancer drugs.
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  • 文章类型: Journal Article
    microRNAs(miRNAs)是一组小的非编码RNA,在控制生命过程中起着重要作用。包括细胞周期控制,凋亡,新陈代谢,发展和分化,导致各种疾病,如神经系统疾病,代谢紊乱,和癌症。化疗被认为是癌症患者的黄金治疗方法。然而,化疗是癌症治疗的主要挑战之一。多柔比星(DOX)是一种抗癌药物,可干扰癌细胞的生长和扩散。DOX用于治疗各种类型的癌症,包括乳房,神经组织,膀胱,胃,子房,甲状腺,肺,骨头,肌肉,关节和软组织癌。最近,miRNA已被鉴定为负责启动化学抗性的机制的特定基因的主要调节因子。miRNAs经由过程调控细胞凋亡对化疗耐药具有调控感化。此外,通过研究证实了miRNAp53基因作为关键肿瘤抑制因子的作用。miRNAs可以影响主要的生物学通路包括PI3K通路。这篇综述旨在介绍目前对miRNAs在细胞凋亡中的作用和机制的认识。p53和PTEN/PI3K/Akt信号通路与DOX抵抗有关。
    MicroRNAs (miRNAs) are a group of small non-coding RNAs and play an important role in controlling vital biological processes, including cell cycle control, apoptosis, metabolism, and development and differentiation, which lead to various diseases such as neurological, metabolic disorders, and cancer. Chemotherapy consider as gold treatment approaches for cancer patients. However, chemotherapeutic is one of the main challenges in cancer management. Doxorubicin (DOX) is an anti-cancer drug that interferes with the growth and spread of cancer cells. DOX is used to treat various types of cancer, including breast, nervous tissue, bladder, stomach, ovary, thyroid, lung, bone, muscle, joint and soft tissue cancers. Also recently, miRNAs have been identified as master regulators of specific genes responsible for the mechanisms that initiate chemical resistance. miRNAs have a regulatory effect on chemotherapy resistance through the regulation of apoptosis process. Also, the effect of miRNAs p53 gene as a key tumor suppressor was confirmed via studies. miRNAs can affect main biological pathways include PI3K pathway. This review aimed to present the current understanding of the mechanisms and effects of miRNAs on apoptosis, p53 and PTEN/PI3K/Akt signaling pathway related to DOX resistance.
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  • 文章类型: Journal Article
    机械力通过多种机制影响牙周健康。通常,机械力可以促进软组织和硬组织的新陈代谢。然而,过度的力量可能会损害牙周组织或导致不可逆的炎症,而没有闭塞力也会导致组织萎缩和骨吸收。我们系统地搜索了PubMed和WebofScience数据库,发现了某些机械力对免疫防御机制,细胞外基质(ECM)代谢,特定的蛋白质,骨代谢,特征性牙周膜干细胞(PDLSCs)和非编码RNA(ncRNAs),因为这些因素有助于牙周稳态。免疫防御功能在力量下发生变化;基因,信号通路和蛋白酶在调节ECM代谢的力作用下发生改变;由于其在机械转导和组织代谢中的重要功能,因此分别讨论了几种特定的蛋白质。骨细胞的功能,成骨细胞,和破骨细胞被激活以维持骨稳态。此外,ncRNAs有可能影响基因表达,改变组织代谢。本文综述了机械力对牙周稳态的所有这些机制。找出根本原因,本综述为力对牙周健康的作用机制提供了新的视角,并为牙周稳态的一些新的研究方向提供了指导。
    Mechanical forces affect periodontal health through multiple mechanisms. Normally, mechanical forces can boost soft and hard tissue metabolism. However, excessive forces may damage the periodontium or result in irreversible inflammation, whereas absence of occlusion forces also leads to tissue atrophy and bone resorption. We systemically searched the PubMed and Web of Science databases and found certain mechanisms of mechanical forces on immune defence, extracellular matrix (ECM) metabolism, specific proteins, bone metabolism, characteristic periodontal ligament stem cells (PDLSCs) and non-coding RNAs (ncRNAs) as these factors contribute to periodontal homeostasis. The immune defence functions change under forces; genes, signalling pathways and proteinases are altered under forces to regulate ECM metabolism; several specific proteins are separately discussed due to their important functions in mechanotransduction and tissue metabolism. Functions of osteocytes, osteoblasts, and osteoclasts are activated to maintain bone homeostasis. Additionally, ncRNAs have the potential to influence gene expression and thereby, modify tissue metabolism. This review summarizes all these mechanisms of mechanical forces on periodontal homeostasis. Identifying the underlying causes, this review provides a new perspective of the mechanisms of force on periodontal health and guides for some new research directions of periodontal homeostasis.
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  • 文章类型: Journal Article
    膀胱癌(BCa)是全球范围内非常普遍的癌症,它导致了许多死亡和疾病病例。由于这种疾病的多样性,有必要进行深入研究分子方面的重要研究,有可能发现新的诊断和治疗方法。最近,对非编码RNA(ncRNAs)的关注显着增加,包括microRNAs(miRNAs),长链非编码RNA(lncRNA),和环状RNAs(circRNAs),由于他们越来越认识到他们参与BCa的进展和表现。由于外泌体具有运输多种活性物质的潜力,因此对外泌体的兴趣大大增加。包括蛋白质,核酸,碳水化合物,和脂质。这些组分的组合基于特定细胞及其条件而不同。研究表明,使用外泌体可以在识别和预测BCa方面具有相当大的优势,提供一种侵入性较小的替代方案。在外泌体中发现的脂质双层膜的独特排列使得它们对于施用旨在管理癌症的治疗特别有效。在这次审查中,我们试图总结参与BCa发病机制的不同ncRNAs。此外,我们强调了外泌体ncRNAs在BCa中的作用。
    Bladder cancer (BCa) is a highly prevalent type of cancer worldwide, and it is responsible for numerous deaths and cases of disease. Due to the diverse nature of this disease, it is necessary to conduct significant research that delves deeper into the molecular aspects, to potentially discover novel diagnostic and therapeutic approaches. Lately, there has been a significant increase in the focus on non-coding RNAs (ncRNAs), including microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs), due to their growing recognition for their involvement in the progression and manifestation of BCa. The interest in exosomes has greatly grown due to their potential for transporting a diverse array of active substances, including proteins, nucleic acids, carbohydrates, and lipids. The combination of these components differs based on the specific cell and its condition. Research indicates that using exosomes could have considerable advantages in identifying and forecasting BCa, offering a less invasive alternative. The distinctive arrangement of the lipid bilayer membrane found in exosomes is what makes them particularly effective for administering treatments aimed at managing cancer. In this review, we have tried to summarize different ncRNAs that are involved in BCa pathogenesis. Moreover, we highlighted the role of exosomal ncRNAs in BCa.
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