long non-coding RNAs

长链非编码 RNA
  • 文章类型: Journal Article
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    人类和细菌之间的对抗正在进行中,对抗细菌感染的策略不断发展。随着RNA测序技术的进步,与细菌感染相关的非编码RNA(ncRNAs)已经引起了极大的关注。最近,长ncRNAs(lncRNAs)已被鉴定为无菌炎症反应和细胞防御的调节因子。它们参与调节细胞核和细胞质中的宿主抗微生物免疫。越来越多的证据表明,lncRNAs对于细菌感染期间宿主和病原体之间复杂的相互作用至关重要。本文着重阐述了lncRNAs在临床标志中的潜在应用,细胞损伤,豁免权,毒力,以及细菌感染中的耐药性。此外,我们讨论了在细菌感染背景下研究lncRNAs的挑战和局限性,并强调了这个有前途的领域的明确方向。
    The confrontation between humans and bacteria is ongoing, with strategies for combating bacterial infections continually evolving. With the advancement of RNA sequencing technology, non-coding RNAs (ncRNAs) associated with bacterial infections have garnered significant attention. Recently, long ncRNAs (lncRNAs) have been identified as regulators of sterile inflammatory responses and cellular defense against live bacterial pathogens. They are involved in regulating host antimicrobial immunity in both the nucleus and cytoplasm. Increasing evidence indicates that lncRNAs are critical for the intricate interactions between host and pathogen during bacterial infections. This paper emphatically elaborates on the potential applications of lncRNAs in clinical hallmarks, cellular damage, immunity, virulence, and drug resistance in bacterial infections in greater detail. Additionally, we discuss the challenges and limitations of studying lncRNAs in the context of bacterial infections and highlight clear directions for this promising field.
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  • 文章类型: Journal Article
    口腔鳞状细胞癌(OSCC)是口腔癌的主要形式,以预后不良为标志。Ferroptosis,一种程序性细胞死亡,在各种癌症的发生和发展中起着至关重要的作用。长链非编码RNA(lncRNAs)在调节癌症发展方面是突出的。然而,在OSCC中铁凋亡相关lncRNAs(FRLs)的预后意义仍未得到充分研究。本研究旨在开发一种基于FRL的预测特征来预测OSCC患者的预后。
    我们从癌症基因组图谱(TCGA)和FerrDb数据库收集了FRL的表达谱以及临床数据。使用LASSO算法进行Cox回归分析,构建了基于10个FRL的预后模型,并对其预测能力进行了评估。然后,该模型用于研究功能富集,免疫景观,m6A基因,体细胞变异,以及不同风险队列患者的药物反应。最后,STARD4-AS1(含4-反义RNA1的类固醇生成急性调节蛋白相关脂质转移结构域)的表达和功能,根据我们的生物信息学分析,OSCC筛查的潜在预后标志物,进行了体外研究。
    我们开发了包含10个FRL的签名,以根据其计算的风险评分将患者分为两个风险队列。与低风险队列中的患者相比,被分类为高风险的患者表现出明显较差的预后。此外,生存分析,患者风险热图,和风险曲线验证了签名的准确性。使用免疫微环境很好地研究了这种特征在OSCC中的作用,突变,和基因集富集分析(GSEA)。此外,七种药物,包括顺铂和多西他赛,被确定为高危癌症患者的潜在治疗方法。此外,在OSCC细胞系中STARD4-AS1的敲低显著抑制细胞增殖和迁移并诱导铁凋亡。
    使用此签名可能会改善OSCC的总体生存预测,为免疫疗法和靶向疗法带来新的启示。此外,STARD4-AS1可能调控OSCC的铁凋亡过程,可作为一种新型的生物标志物。
    UNASSIGNED: Oral squamous cell carcinoma (OSCC) stands as the predominant form of oral cancer, marked by a poor prognosis. Ferroptosis, a type of programmed cell death, plays a critical role in the initiation and progression of various cancers. Long non-coding RNAs (lncRNAs) are prominent in modulating cancer development. Nevertheless, the prognostic significance of ferroptosis-related lncRNAs (FRLs) in OSCC remains inadequately explored. This study aims to develop a predictive signature based on FRLs to forecast the prognosis of OSCC patients.
    UNASSIGNED: We gathered expression profiles of FRLs along with clinical data from The Cancer Genome Atlas (TCGA) and FerrDb databases. A prognostic model based on 10 FRLs were constructed using Cox regression analyses with LASSO algorithms, and their predictive power was evaluated. Then, the model was used to investigate functional enrichment, immune landscape, m6A genes, somatic variations, and drug response in different risk cohorts of patients. Finally, the expression and function of STARD4-AS1 (steroidogenic acute regulator protein-related lipid transfer domain containing 4-antisense RNA 1), a potential prognostic marker for OSCC screening based on our bioinformatics analysis, were investigated in vitro.
    UNASSIGNED: We developed a signature comprising 10 FRLs to stratify patients into two risk cohorts according to their calculated risk scores. Patients classified as high-risk exhibited significantly poorer prognoses compared to those in the low-risk cohort. Furthermore, survival analysis, patient risk heat plot, and risk curve verified the accuracy of the signature. The role of this signature in OSCC was well investigated using immune microenvironment, mutational, and gene set enrichment analysis (GSEA). Moreover, seven drugs, including cisplatin and docetaxel, were identified as potential treatments for patients with high-risk cancers. In addition, the knockdown of STARD4-AS1 in OSCC cell lines markedly inhibited cell proliferation and migration and induced ferroptosis.
    UNASSIGNED: Using this signature may improve overall survival predictions in OSCC, throwing new light on immunotherapies and targeted therapies. Moreover, STARD4-AS1 might regulate the process of ferroptosis and could be used as a novel biomarker of OSCC.
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  • 文章类型: Journal Article
    胶质母细胞瘤在原发性脑肿瘤中提出了巨大的挑战:其致瘤干细胞,能够自我更新,扩散,和差异化,对肿瘤发生和治疗抵抗有很大贡献。这些胶质母细胞瘤干细胞(GSC),类似于传统的干细胞和祖细胞,采用对组织发育和修复至关重要的途径,促进肿瘤不间断的扩张。长链非编码RNA(lncRNA),人类转录组的重要组成部分,它们在正常生理过程和癌症发病机理中的关键作用引起了相当大的兴趣。它们显示细胞或组织特异性表达模式,广泛的研究强调了它们对调节GSC特性和细胞分化的影响,从而为治疗干预提供了有希望的途径。因此,lncRNAs,它们能够对肿瘤的发生和发展施加调控控制,已经成为创新的胶质母细胞瘤治疗的有希望的目标。这篇综述探讨了GSC相关lncRNAs的值得注意的例子,并阐明了它们在驱动胶质母细胞瘤进展中的功能作用。此外,我们深入研究了利用3D体外模型来研究GSC生物学,并阐明了靶向lncRNAs作为治疗胶质母细胞瘤的潜在疗法的四种主要方法。
    Glioblastoma poses a formidable challenge among primary brain tumors: its tumorigenic stem cells, capable of self-renewal, proliferation, and differentiation, contribute substantially to tumor initiation and therapy resistance. These glioblastoma stem cells (GSCs), resembling conventional stem and progenitor cells, adopt pathways critical for tissue development and repair, promoting uninterrupted tumor expansion. Long non-coding RNAs (lncRNAs), a substantial component of the human transcriptome, have garnered considerable interest for their pivotal roles in normal physiological processes and cancer pathogenesis. They display cell- or tissue-specific expression patterns, and extensive investigations have highlighted their impact on regulating GSC properties and cellular differentiation, thus offering promising avenues for therapeutic interventions. Consequently, lncRNAs, with their ability to exert regulatory control over tumor initiation and progression, have emerged as promising targets for innovative glioblastoma therapies. This review explores notable examples of GSC-associated lncRNAs and elucidates their functional roles in driving glioblastoma progression. Additionally, we delved deeper into utilizing a 3D in vitro model for investigating GSC biology and elucidated four primary methodologies for targeting lncRNAs as potential therapeutics in managing glioblastoma.
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  • 文章类型: Journal Article
    免疫检查点抑制剂(ICIs)表现出持久的反应,长期生存益处,与化疗相比,癌症患者的预后有所改善。然而,大多数癌症患者对ICI没有反应,对ICI治疗有反应的患者中有很大比例会对ICI产生先天或后天的耐药性,限制其临床效用。研究最多的ICI反应的预测组织生物标志物是PD-L1免疫组织化学表达,DNA错配修复缺陷,和肿瘤突变负担,尽管这些是ICI反应的弱预测因子。更好的预测性生物标志物的鉴定仍然是改善将受益于ICI的患者的鉴定的重要目标。这里,我们回顾了ICI反应的已建立和新兴的生物标志物,关注癌症患者的表观基因组和基因组改变,它们有可能帮助指导单药ICI免疫治疗或ICI免疫治疗与其他ICI免疫治疗或药物的组合。我们简要回顾了ICI反应生物标志物的现状,包括研究性生物标志物,我们提出了一些新兴的和有前途的表观基因组生物标志物候选的见解,包括目前在黑色素瘤患者ICI免疫治疗反应方面的知识差距。
    Immune checkpoint inhibitors (ICIs) demonstrate durable responses, long-term survival benefits, and improved outcomes in cancer patients compared to chemotherapy. However, the majority of cancer patients do not respond to ICIs, and a high proportion of those patients who do respond to ICI therapy develop innate or acquired resistance to ICIs, limiting their clinical utility. The most studied predictive tissue biomarkers for ICI response are PD-L1 immunohistochemical expression, DNA mismatch repair deficiency, and tumour mutation burden, although these are weak predictors of ICI response. The identification of better predictive biomarkers remains an important goal to improve the identification of patients who would benefit from ICIs. Here, we review established and emerging biomarkers of ICI response, focusing on epigenomic and genomic alterations in cancer patients, which have the potential to help guide single-agent ICI immunotherapy or ICI immunotherapy in combination with other ICI immunotherapies or agents. We briefly review the current status of ICI response biomarkers, including investigational biomarkers, and we present insights into several emerging and promising epigenomic biomarker candidates, including current knowledge gaps in the context of ICI immunotherapy response in melanoma patients.
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    芥菜(BrassicajunceaL.Czern和Coss),一种重要的蔬菜作物,由于季节性干旱压力,经历了明显的逆境,特别是在种子发芽阶段。虽然对干旱响应基因有部分理解,长链非编码RNA(lncRNAs)在调节芥菜的干旱胁迫反应中的作用在很大程度上尚未被研究。在这项研究中,我们表明,与干旱易感品种“水东”相比,耐旱品种“威良”表现出明显较低的基础水势(-1.073MPavs-0.437MPa)和较高的发芽率(41.2%vs0%)。干旱条件下。高通量RNA测序技术揭示了干旱胁迫下萌发过程中来自两个品种的lncRNAs的大量库。结果鉴定了2,087个差异表达的lncRNAs(DELs)及其相应连接的12,433个靶基因。注意到DEL靶向的84个基因在光合作用途径中表现出富集。基因网络的构建表明,MSTRG.150397,一种调控lncRNA,被推断可能调节关键的光合基因(Psb27,PetC,PetH,和PsbW),而MSTRG.107159被指示为六个干旱响应性PIP基因的抑制调节因子。Further,加权基因共表达网络分析(WGCNA)证实了所确定的DEL靶向的光强度和应激反应基因的参与。通过qPCR验证了lncRNA的精确性和调控影响。这项研究扩展了我们对芥菜干旱胁迫反应调控机制的认识,这将有助于提高这种作物耐旱性的策略。
    Leaf mustard (Brassica juncea L. Czern & Coss), an important vegetable crop, experiences pronounced adversity due to seasonal drought stress, particularly at the seed germination stage. Although there is partial comprehension of drought-responsive genes, the role of long non-coding RNAs (lncRNAs) in adjusting mustard\'s drought stress response is largely unexplored. In this study, we showed that the drought-tolerant cultivar \'Weiliang\' manifested a markedly lower base water potential (-1.073 MPa vs -0.437 MPa) and higher germination percentage (41.2% vs 0%) than the drought-susceptible cultivar \'Shuidong\' under drought conditions. High throughput RNA sequencing techniques revealed a significant repertoire of lncRNAs from both cultivars during germination under drought stress, resulting in the identification of 2,087 differentially expressed lncRNAs (DELs) and their correspondingly linked 12,433 target genes. It was noted that 84 genes targeted by DEL exhibited enrichment in the photosynthesis pathway. Gene network construction showed that MSTRG.150397, a regulatory lncRNA, was inferred to potentially modulate key photosynthetic genes (Psb27, PetC, PetH, and PsbW), whilst MSTRG.107159 was indicated as an inhibitory regulator of six drought-responsive PIP genes. Further, weighted gene co-expression network analysis (WGCNA) corroborated the involvement of light intensity and stress response genes targeted by the identified DELs. The precision and regulatory impact of lncRNA were verified through qPCR. This study extends our knowledge of the regulatory mechanisms governing drought stress responses in mustard, which will help strategies to augment drought tolerance in this crop.
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  • 文章类型: Journal Article
    近年来,新兴的研究强调了非编码RNA在协调生长中的关键作用,发展,以及各种疾病在生物体中的发病机理。然而,尽管取得了这些进步,我们对长非编码RNA(lncRNA)和环状RNA(circRNA)对晶状体发育的具体贡献的理解仍然十分有限.澄清复杂的基因调控网络对于解开晶状体相关疾病的分子基础至关重要。在这项研究中,我们旨在通过对信使RNA(mRNA)的表达谱进行全面分析来解决这一差距,lncRNAs,和circRNAs在小鼠晶状体的关键发育时间点,包括胚胎(E10.5,E12.5和E16.5)和出生后阶段(P0.5,P10.5和P60)。利用RNA测序技术,我们确定了对晶状体发育至关重要的关键转录本。我们的分析揭示了差异表达(DE)mRNA,lncRNAs,和circRNAs跨越不同的发育阶段。特别值得注意的是,有1831个共差异表达(CO-DE)mRNA,150CO-DElncRNAs,和13个在胚胎阶段鉴定的CO-DEcircRNAs。基因本体论(GO)富集分析揭示了主要与晶状体发育有关的关联,DNA构象变化,和DEmRNAs和lncRNAs之间的血管生成。此外,采用蛋白质-蛋白质相互作用网络,mRNA-lncRNA共表达网络,和circRNA-microRNA-mRNA网络,我们预测了与晶状体发育有关的候选关键分子.我们的发现强调了lncRNAs和circRNAs在这个过程中的关键作用,为晶状体相关疾病的发病机制提供了新的见解,并为该领域的未来探索铺平了道路。
    In recent years, burgeoning research has underscored the pivotal role of non-coding RNA in orchestrating the growth, development, and pathogenesis of various diseases across organisms. However, despite these advances, our understanding of the specific contributions of long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs) to lens development remains notably limited. Clarifying the intricate gene regulatory networks is imperative for unraveling the molecular underpinnings of lens-related disorders. In this study, we aimed to address this gap by conducting a comprehensive analysis of the expression profiles of messenger RNAs (mRNAs), lncRNAs, and circRNAs at critical developmental time points of the mouse lens, encompassing both embryonic (E10.5, E12.5, and E16.5) and postnatal stages (P0.5, P10.5, and P60). Leveraging RNA-sequencing technology, we identified key transcripts pivotal to lens development. Our analysis revealed differentially expressed (DE) mRNAs, lncRNAs, and circRNAs across various developmental stages. Particularly noteworthy, there were 1831 co-differentially expressed (CO-DE) mRNAs, 150 CO-DE lncRNAs, and 13 CO-DE circRNAs identified during embryonic stages. Gene Ontology (GO) enrichment analysis unveiled associations primarily related to lens development, DNA conformational changes, and angiogenesis among DE mRNAs and lncRNAs. Furthermore, employing protein-protein interaction networks, mRNA-lncRNA co-expression networks, and circRNA-microRNA-mRNA networks, we predicted candidate key molecules implicated in lens development. Our findings underscore the pivotal roles of lncRNAs and circRNAs in this process, offering fresh insights into the pathogenesis of lens-related disorders and paving the way for future exploration in this field.
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  • 文章类型: Journal Article
    最近的研究已经解决了长链非编码RNA(lnc-RNA)的可能作用,转移相关肺腺癌转录本1(MALAT1),和牛磺酸上调基因1(TUG1),调节肥胖相关代谢异常的潜在机制。然而,研究是有限和矛盾的。因此,我们试图研究肥胖和超重女性中这两种lnc-RNA的转录水平与代谢综合征(MetS)相关参数的关系.
    这项横断面研究是对342名肥胖和超重的女性进行的。我们进行了包括人体测量的评估,身体成分分析,空腹血糖(FBS)水平,脂质分析,胰岛素水平,HOMA-IR指数,和肝脏酶谱.定量实时聚合酶链反应(PCR)用于评估MALAT1和TUG1的转录水平。此外,使用147个问题的半定量食物频率问卷(FFQ)和国际身体活动问卷(IPAQ)来评估食物摄入量和身体活动,分别。
    FBS与MALAT1转录水平之间存在显着关联(β:0.382;95%CI:0.124,0.640;P=0.004)。此外,甘油三酯(TG)与MALAT1转录水平之间存在显著相关性(β:4.767;95%CI:2.803,6.731;P<0.0001)。在调整了年龄之后,BMI,能量摄入,和身体活动,高密度脂蛋白胆固醇(HDL-c)与MALAT1转录水平呈负相关(β:-0.325;95%CI:-0.644,-0.006;P=0.046).
    我们的研究结果表明MALAT1mRNA水平与MetS相关参数呈正相关,包括FBG,TG,HDL,超重和肥胖女性的收缩压。然而,需要大量的前瞻性研究来进一步确立这一概念。
    在线版本包含补充材料,可在10.1007/s40200-023-01367-2获得。
    UNASSIGNED: Recent studies have addressed the possible role of long non-coding RNAs (lnc-RNAs), Metastasis-Associated Lung Adenocarcinoma Transcript 1 (MALAT1), and Taurine Upregulated Gene 1 (TUG1), in modulating the underlying mechanisms of obesity-related metabolic abnormalities. However, studies are limited and contradictory. Hence, we sought to investigate the relationship of the transcript level of these two lnc-RNAs with metabolic syndrome (MetS)-related parameters in women with obesity and overweight.
    UNASSIGNED: This cross-sectional study was conducted on 342 women with obese and overweight. We conducted assessments encompassing anthropometric measurements, body composition analysis, fasting blood sugar (FBS) levels, lipid profile analysis, insulin levels, HOMA-IR index, and liver enzyme profiling. A quantitative real-time polymerase chain reaction (PCR) was used to evaluate transcript levels of MALAT1 and TUG1. Also, a 147-question semi-quantitative food frequency questionnaire (FFQ) and the International Physical Activity Questionnaire (IPAQ) were used to evaluate food intake and physical activity, respectively.
    UNASSIGNED: There was a significant association between FBS and MALAT1 transcript level (β: 0.382; 95% CI: 0.124, 0.640; P = 0.004). Also, there was a significant association between triglyceride (TG) and MALAT1 transcript level (β: 4.767; 95% CI: 2.803, 6.731; P < 0.0001). After adjusting for age, BMI, energy intake, and physical activity, an inverse significant association was observed between high-density lipoprotein cholesterol (HDL-c) and MALAT1 transcript level (β: -0.325; 95% CI: -0.644, -0.006; P = 0.046).
    UNASSIGNED: Our findings indicated positive associations between mRNA levels of MALAT1 and MetS-related parameters, including FBG, TG, HDL, and systolic blood pressure in overweight and obese women. However, large prospective studies are needed to further establish this concept.
    UNASSIGNED: The online version contains supplementary material available at 10.1007/s40200-023-01367-2.
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  • 文章类型: Journal Article
    中风是世界上对死亡和永久性残疾最负责的神经系统疾病之一。不同的因素,如血栓,栓子和动脉粥样硬化,参与中风的复杂病理生理学。理解参与这一机制的分子过程对于开发新的,具体和有效的治疗。一些常见的机制是兴奋毒性和钙超载,氧化应激和神经炎症。此外,非编码RNA(ncRNAs)在脑缺血后的病理生理和恢复中至关重要。ncRNAs,特别是microRNA,长链非编码RNA(lncRNAs)对血管生成和神经保护至关重要,它们被认为是治疗性的,脑血管疾病的诊断和预后工具,包括中风。本文综述了缺血性和出血性中风的复杂分子机制,并探讨了miRNAs在脑损伤发展中的作用。此外,除了传统的中风疗法外,我们还将分析基于分子机制的治疗新视角。
    Stroke represents one of the neurological diseases most responsible for death and permanent disability in the world. Different factors, such as thrombus, emboli and atherosclerosis, take part in the intricate pathophysiology of stroke. Comprehending the molecular processes involved in this mechanism is crucial to developing new, specific and efficient treatments. Some common mechanisms are excitotoxicity and calcium overload, oxidative stress and neuroinflammation. Furthermore, non-coding RNAs (ncRNAs) are critical in pathophysiology and recovery after cerebral ischemia. ncRNAs, particularly microRNAs, and long non-coding RNAs (lncRNAs) are essential for angiogenesis and neuroprotection, and they have been suggested to be therapeutic, diagnostic and prognostic tools in cerebrovascular diseases, including stroke. This review summarizes the intricate molecular mechanisms underlying ischemic and hemorrhagic stroke and delves into the function of miRNAs in the development of brain damage. Furthermore, we will analyze new perspectives on treatment based on molecular mechanisms in addition to traditional stroke therapies.
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  • 文章类型: Journal Article
    随着基因检测技术的发展,我们发现了许多不同的基因,lncRNA就是其中之一。LncRNAs是指长度超过200bp的非蛋白质编码RNA分子。是LUAD等人类恶性疾病研究的重点之一。LncRNAs作为癌基因或抑制剂调节肿瘤的发生和进展。LncRNAs的差异表达通过影响细胞增殖促进或抑制肺腺癌的进展,转移,入侵,和细胞凋亡,从而影响患者的预后和生存率。因此,LncRNAs可以作为癌症诊断和治疗的潜在靶点。通过检测肿瘤标志物对该病进行早期诊断。由于肺腺癌早期不易诊断,肿瘤标志物容易忽视,LncRNAs在肺腺癌的诊断和治疗中起着重要作用。本文的主要目的是总结LncRNAs对肺腺癌的已知作用,LncRNAs差异表达对肺腺癌进展的影响,以及相关的信号转导通路。并为今后肺腺癌相关LncRNAs的研究提供新的思路。
    With the development of gene testing technology, we have found many different genes, and lncRNA is one of them. LncRNAs refer to a non-protein coding RNA molecule with a length of more than 200bp, which is one of the focuses of research on human malignant diseases such as LUAD. LncRNAs act as an oncogene or inhibitor to regulate the occurrence and progression of tumors. The differential expression of LncRNAs promotes or inhibits the progression of lung adenocarcinoma by affecting cell proliferation, metastasis, invasion, and apoptosis, thus affecting the prognosis and survival rate of patients. Therefore, LncRNAs can be used as a potential target for diagnosis and treatment of cancer. The early diagnosis of the disease was made through the detection of tumor markers. Because lung adenocarcinoma is not easy to diagnose in the early stage and tumor markers are easy to ignore, LncRNAs play an important role in the diagnosis and treatment of lung adenocarcinoma. The main purpose of this article is to summarize the known effects of LncRNAs on lung adenocarcinoma, the effect of differential expression of LncRNAs on the progression of lung adenocarcinoma, and related signal transduction pathways. And to provide a new idea for the future research of lung adenocarcinoma-related LncRNAs.
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