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Investigation of Antihypertensive Properties of Chios Mastic via Monitoring microRNA-21 Expression Levels in the Plasma of Well-Controlled Hypertensive Patients. 通过监测控制良好的高血压患者血浆中 microRNA-21 的表达水平研究奇奥果胶的降压特性
IF 3.6 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-05-31 DOI: 10.3390/ncrna10030033
Maria Tsota, Panagiota Giardoglou, Evangelia Mentsiou-Nikolaou, Panagiotis Symianakis, Ioanna Panagiota Kalafati, Anastasia-Areti Kyriazopoulou-Korovesi, Lasthenis Angelidakis, Maria Papaioannou, Christina Konstantaki, Hyper-Mastic Consortium, Kimon Stamatelopoulos, George V Dedoussis

Hypertension is a chronic, multifactorial disease, leading to high cardiovascular morbidity and mortality globally. Despite the advantages of pharmaceutical treatments, natural products have gained scientific interest due to their emerging phytotherapeutic properties. Chios mastic is a natural Greek product, consisting of bioactive compounds which modify microRNAs' (small, expression-regulating molecules) expression. In this study, we investigated the antihypertensive properties of Chios mastic through the assessment of miR-21 levels. Herein, plasma samples of 57 individuals with hypertension, recruited for the purposes of the HYPER-MASTIC study, were analyzed. This was a clinical trial with Chios mastic supplements in which the patients were divided into groups receiving high and low mastic doses and placebo supplements, respectively. miR-21 was significantly upregulated in patients compared to normotensive individuals. Mean changes in miR-21 levels were statistically significant, after adjusting for sex and age, between the placebo and low-dose group and between the low- and high-dose group. Post-intervention miR-21 levels were positively associated with night-time systolic blood pressure, pulse pressure, and central systolic mean arterial pressure and negatively associated with night-time pulse wave velocity in the low-dose group. Our findings suggest a potential implication of miR-21 in the association of Chios mastic with night-time blood pressure measurements.

高血压是一种慢性、多因素疾病,导致全球心血管疾病发病率和死亡率居高不下。尽管药物治疗有其优势,但天然产品因其新兴的植物治疗特性而受到科学界的关注。希俄斯胶泥是希腊的一种天然产品,由生物活性化合物组成,可改变微 RNA(调节表达的小分子)的表达。在这项研究中,我们通过评估 miR-21 的水平,研究了希俄斯胶浆的抗高血压特性。在此,我们分析了 57 名高血压患者的血浆样本,这些患者是为了参加 HYPER-MASTIC 研究而被招募的。与正常血压的人相比,患者的 miR-21 明显上调。在对性别和年龄进行调整后,安慰剂组和低剂量组之间以及低剂量组和高剂量组之间的 miR-21 水平的平均变化具有统计学意义。在低剂量组中,干预后的 miR-21 水平与夜间收缩压、脉压和中心收缩平均动脉压呈正相关,而与夜间脉搏波速度呈负相关。我们的研究结果表明,miR-21 对奇奥斯胶原蛋白与夜间血压测量的关系具有潜在的影响。
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引用次数: 0
MEF2C Directly Interacts with Pre-miRNAs and Distinct RNPs to Post-Transcriptionally Regulate miR-23a-miR-27a-miR-24-2 microRNA Cluster Member Expression MEF2C 直接与 pre-miRNA 和不同的 RNPs 相互作用,转录后调控 miR-23a-miR-27a-miR-24-2 microRNA 簇成员的表达
IF 4.3 Q1 Biochemistry, Genetics and Molecular Biology Pub Date : 2024-05-17 DOI: 10.3390/ncrna10030032
E. Lozano-Velasco, C. García-Padilla, Miguel Carmona-Garcia, Alba Gonzalez-Diaz, Angela Arequipa-Rendon, A. Aránega, Diego Franco
Transcriptional regulation constitutes a key step in gene expression regulation. Myocyte enhancer factor 2C (MEF2C) is a transcription factor of the MADS box family involved in the early development of several cell types, including muscle cells. Over the last decade, a novel layer of complexity modulating gene regulation has emerged as non-coding RNAs have been identified, impacting both transcriptional and post-transcriptional regulation. microRNAs represent the most studied and abundantly expressed subtype of small non-coding RNAs, and their functional roles have been widely documented. On the other hand, our knowledge of the transcriptional and post-transcriptional regulatory mechanisms that drive microRNA expression is still incipient. We recently demonstrated that MEF2C is able to transactivate the long, but not short, regulatory element upstream of the miR-23a-miR-27a-miR-24-2 transcriptional start site. However, MEF2C over-expression and silencing, respectively, displayed distinct effects on each of the miR-23a-miR-27a-miR-24-2 mature cluster members without affecting pri-miRNA expression levels, thus supporting additional MEF2C-driven regulatory mechanisms. Within this study, we demonstrated a complex post-transcriptional regulatory mechanism directed by MEF2C in the regulation of miR-23a-miR-27a-miR-24-2 cluster members, distinctly involving different domains of the MEF2C transcription factor and the physical interaction with pre-miRNAs and Ksrp, HnRNPa3 and Ddx17 transcripts.
转录调控是基因表达调控的关键步骤。肌细胞增强因子 2C(MEF2C)是 MADS 盒家族的一个转录因子,参与了包括肌肉细胞在内的多种细胞类型的早期发育。过去十年中,随着非编码 RNA 的发现,基因调控出现了一层新的复杂性,对转录和转录后调控都产生了影响。microRNA 是研究最多、表达最丰富的小型非编码 RNA 亚型,其功能作用已被广泛记录。另一方面,我们对驱动 microRNA 表达的转录和转录后调控机制的了解仍处于起步阶段。我们最近证实,MEF2C 能够反式激活 miR-23a-miR-27a-miR-24-2 转录起始位点上游的长调控元件,但不能激活短调控元件。然而,MEF2C的过度表达和沉默分别对每个miR-23a-miR-27a-miR-24-2成熟簇成员显示出不同的影响,而不影响pri-miRNA的表达水平,从而支持MEF2C驱动的其他调控机制。在这项研究中,我们证明了 MEF2C 在调控 miR-23a-miR-27a-miR-24-2 簇成员时引导的复杂的转录后调控机制,其中明显涉及 MEF2C 转录因子的不同结构域以及与 pre-miRNA 和 Ksrp、HnRNPa3 和 Ddx17 转录本的物理相互作用。
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引用次数: 0
The RNAi Machinery in the Fungus Fusarium fujikuroi Is Not Very Active in Synthetic Medium and Is Related to Transposable Elements 真菌 Fusarium fujikuroi 中的 RNAi 机制在合成介质中并不十分活跃,且与可转座元件有关
IF 4.3 Q1 Biochemistry, Genetics and Molecular Biology Pub Date : 2024-05-16 DOI: 10.3390/ncrna10030031
Javier Pardo-Medina, Tim A. Dahlmann, Minou Nowrousian, M. Carmen Limón, Javier Avalos
Small RNAS (sRNAs) participate in regulatory RNA interference (RNAi) mechanisms in a wide range of eukaryotic organisms, including fungi. The fungus Fusarium fujikuroi, a model for the study of secondary metabolism, contains a complete set of genes for RNAi pathways. We have analyzed by high-throughput sequencing the content of sRNAs in total RNA samples of F. fujikuroi grown in synthetic medium in the dark or after 1 h of illumination, using libraries below 150 nt, covering sRNAs and their precursors. For comparison, a parallel analysis with Fusarium oxysporum was carried out. The sRNA reads showed a higher proportion of 5′ uracil in the RNA samples of the expected sizes in both species, indicating the occurrence of genuine sRNAs, and putative miRNA-like sRNAs (milRNAS) were identified with prediction software. F. fujikuroi carries at least one transcriptionally expressed Ty1/copia-like retrotransposable element, in which sRNAs were found in both sense and antisense DNA strands, while in F. oxysporum skippy-like elements also show sRNA formation. The finding of sRNA in these mobile elements indicates an active sRNA-based RNAi pathway. Targeted deletion of dcl2, the only F. fujikuroi Dicer gene with significant expression under the conditions tested, did not produce appreciable phenotypic or transcriptomic alterations.
小 RNAS(sRNA)参与了包括真菌在内的多种真核生物的 RNA 干扰(RNAi)调控机制。真菌 Fusarium fujikuroi 是研究次生代谢的模型,它含有一套完整的 RNAi 通路基因。我们利用 150 nt 以下的文库,通过高通量测序分析了在合成培养基中黑暗或光照 1 小时后生长的 F. fujikuroi 总 RNA 样本中 sRNA 的含量,涵盖了 sRNA 及其前体。为了进行比较,还与 Fusarium oxysporum 进行了平行分析。在这两个物种中,sRNA 读数显示,在预期大小的 RNA 样本中,5′尿嘧啶的比例较高,这表明存在真正的 sRNA,并通过预测软件鉴定出了假定的 miRNA 样 sRNA(milRNAS)。F. fujikuroi携带至少一个转录表达的Ty1/copia样逆转录转座元件,在其中的有义和反义DNA链中都发现了sRNA,而在F. oxysporum的skippy样元件中也有sRNA形成。在这些可移动元件中发现 sRNA 表明存在一种活跃的基于 sRNA 的 RNAi 途径。dcl2 是在测试条件下唯一有显著表达的 F. fujikuroi Dicer 基因,靶向删除 dcl2 并没有产生明显的表型或转录组变化。
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引用次数: 0
A Systematic Review and Meta-Analysis of microRNA Profiling Studies in Chronic Kidney Diseases 慢性肾脏病中 microRNA 图谱研究的系统性回顾和元分析
IF 4.3 Q1 Biochemistry, Genetics and Molecular Biology Pub Date : 2024-05-03 DOI: 10.3390/ncrna10030030
Gantsetseg Garmaa, S. Bunduc, T. Kói, Péter Hegyi, D. Csupor, Dariimaa Ganbat, F. Dembrovszky, F. Meznerics, Ailar Nasirzadeh, C. Barbagallo, G. Kökény
Chronic kidney disease (CKD) represents an increasing health burden. Evidence suggests the importance of miRNA in diagnosing CKD, yet the reports are inconsistent. This study aimed to determine novel miRNA biomarkers and potential therapeutic targets from hypothesis-free miRNA profiling studies in human and murine CKDs. Comprehensive literature searches were conducted on five databases. Subgroup analyses of kidney diseases, sample types, disease stages, and species were conducted. A total of 38 human and 12 murine eligible studies were analyzed using Robust Rank Aggregation (RRA) and vote-counting analyses. Gene set enrichment analyses of miRNA signatures in each kidney disease were conducted using DIANA-miRPath v4.0 and MIENTURNET. As a result, top target genes, Gene Ontology terms, the interaction network between miRNA and target genes, and molecular pathways in each kidney disease were identified. According to vote-counting analysis, 145 miRNAs were dysregulated in human kidney diseases, and 32 were dysregulated in murine CKD models. By RRA, miR-26a-5p was significantly reduced in the kidney tissue of Lupus nephritis (LN), while miR-107 was decreased in LN patients’ blood samples. In both species, epithelial-mesenchymal transition, Notch, mTOR signaling, apoptosis, G2/M checkpoint, and hypoxia were the most enriched pathways. These miRNA signatures and their target genes must be validated in large patient cohort studies.
慢性肾脏病(CKD)对健康造成的负担与日俱增。有证据表明 miRNA 在诊断 CKD 中的重要性,但相关报道并不一致。本研究旨在从人类和鼠类 CKD 的无假设 miRNA 图谱研究中确定新型 miRNA 生物标记物和潜在治疗靶点。研究人员在五个数据库中进行了全面的文献检索。对肾脏疾病、样本类型、疾病阶段和物种进行了分组分析。采用稳健等级聚合(RRA)和计票分析法对符合条件的 38 项人类研究和 12 项鼠类研究进行了分析。利用 DIANA-miRPath v4.0 和 MIENTURNET 对每种肾病的 miRNA 特征进行了基因组富集分析。结果确定了每种肾病的顶级靶基因、基因本体术语、miRNA 与靶基因之间的相互作用网络和分子通路。根据计票分析,145 个 miRNA 在人类肾脏疾病中出现失调,32 个 miRNA 在小鼠 CKD 模型中出现失调。通过RRA,狼疮性肾炎(LN)肾组织中的miR-26a-5p明显减少,而LN患者血液样本中的miR-107减少。在这两个物种中,上皮-间质转化、Notch、mTOR 信号转导、细胞凋亡、G2/M 检查点和缺氧是最富集的通路。这些miRNA特征及其靶基因必须在大型患者队列研究中得到验证。
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引用次数: 0
Dysregulation of a Subset of Circulating and Vesicle-Associated miRNA in Pancreatic Cancer 胰腺癌中循环和囊泡相关 miRNA 亚群的调控失调
IF 4.3 Q1 Biochemistry, Genetics and Molecular Biology Pub Date : 2024-05-01 DOI: 10.3390/ncrna10030029
Giulia Girolimetti, Iulia Andreea Pelisenco, L. Eusebi, Claudio Ricci, Beatrice Cavina, Ivana Kurelac, T. Verri, Matteo Calcagnile, Pietro Alifano, Alessandro Salvi, Cecilia Bucci, Flora Guerra
Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive neoplasia, characterized by early metastasis, low diagnostic rates at early stages, resistance to drugs, and poor prognosis. There is an urgent need to better characterize this disease in order to identify efficient diagnostic/prognostic biomarkers. Since microRNAs (miRNAs) contribute to oncogenesis and metastasis formation in PDAC, they are considered potential candidates for fulfilling this task. In this work, the levels of two miRNA subsets (involved in chemoresistance or with oncogenic/tumor suppressing functions) were investigated in a panel of PDAC cell lines and liquid biopsies of a small cohort of patients. We used RT-qPCR and droplet digital PCR (ddPCR) to measure the amounts of cellular- and vesicle-associated, and circulating miRNAs. We found that both PDAC cell lines, also after gemcitabine treatment, and patients showed low amounts of cellular-and vesicle-associated miR-155-5p, compared to controls. Interestingly, we did not find any differences when we analyzed circulating miR-155-5p. Furthermore, vesicle-related miR-27a-3p increased in cancer patients compared to the controls, while circulating let-7a-5p, miR-221-3p, miR-23b-3p and miR-193a-3p presented as dysregulated in patients compared to healthy individuals. Our results highlight the potential clinical significance of these analyzed miRNAs as non-invasive diagnostic molecular tools to characterize PDAC.
胰腺导管腺癌(PDAC)是侵袭性最强的肿瘤之一,其特点是转移早、早期诊断率低、耐药和预后差。目前迫切需要更好地描述这种疾病的特征,以确定有效的诊断/预后生物标志物。由于微小RNA(miRNA)在PDAC的肿瘤发生和转移形成中起着重要作用,因此被认为是完成这一任务的潜在候选者。在这项研究中,我们在一组 PDAC 细胞系和一小群患者的液体活检组织中调查了两种 miRNA 亚群(参与化疗抵抗或具有致癌/抑瘤功能)的水平。我们采用 RT-qPCR 和液滴数字 PCR (ddPCR) 技术测量了细胞、囊泡相关和循环 miRNA 的数量。我们发现,与对照组相比,同样经过吉西他滨治疗的 PDAC 细胞系和患者的细胞与囊泡相关 miR-155-5p 含量都很低。有趣的是,我们在分析循环 miR-155-5p 时没有发现任何差异。此外,与对照组相比,癌症患者与囊泡相关的 miR-27a-3p 增加了,而与健康人相比,患者循环中的 let-7a-5p、miR-221-3p、miR-23b-3p 和 miR-193a-3p 出现了失调。我们的研究结果凸显了这些被分析的 miRNAs 作为非侵入性诊断分子工具来描述 PDAC 特征的潜在临床意义。
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引用次数: 0
Identification and Functional Characterization of Alternative Transcripts of LncRNA HNF1A-AS1 and Their Impacts on Cell Growth, Differentiation, Liver Diseases, and in Response to Drug Induction. LncRNA HNF1A-AS1 替代转录本的鉴定和功能表征及其对细胞生长、分化、肝脏疾病和药物诱导的影响。
IF 4.3 Q1 Biochemistry, Genetics and Molecular Biology Pub Date : 2024-04-21 DOI: 10.3390/ncrna10020028
Jing Jin, Le Tra Giang Nguyen, Andrew Wassef, Ragui Sadek, Timothy M Schmitt, Grace L Guo, Theodore P Rasmussen, Xiao-Bo Zhong

The long non-coding RNA (lncRNA) hepatocyte nuclear factor-1 alpha (HNF1A) antisense RNA 1 (HNF1A-AS1) is an important lncRNA for liver growth, development, cell differentiation, and drug metabolism. Like many lncRNAs, HNF1A-AS1 has multiple annotated alternative transcripts in the human genome. Several fundamental biological questions are still not solved: (1) How many transcripts really exist in biological samples, such as liver samples and liver cell lines? (2) What are the expression patterns of different alternative HNF1A-AS1 transcripts at different conditions, including during cell growth and development, after exposure to xenobiotics (such as drugs), and in disease conditions, such as metabolic dysfunction-associated steatotic liver disease (MASLD), alcohol-associated liver disease (ALD) cirrhosis, and obesity? (3) Does the siRNA used in previous studies knock down one or multiple transcripts? (4) Do different transcripts have the same or different functions for gene regulation? The presented data confirm the existence of several annotated HNF1A-AS1 transcripts in liver samples and cell lines, but also identify some new transcripts, which are not annotated in the Ensembl genome database. Expression patterns of the identified HNF1A-AS1 transcripts are highly correlated with the cell differentiation of matured hepatocyte-like cells from human embryonic stem cells (hESC), growth and differentiation of HepaRG cells, in response to rifampicin induction, and in various liver disease conditions. The expression levels of the HNF1A-AS1 transcripts are also highly correlated to the expression of cytochrome P450 enzymes, such as CYP3A4, during HepaRG growth, differentiation, and in response to rifampicin induction.

长非编码 RNA(lncRNA)肝细胞核因子-1α(HNF1A)反义 RNA 1(HNF1A-AS1)是肝脏生长、发育、细胞分化和药物代谢的重要 lncRNA。与许多 lncRNA 一样,HNF1A-AS1 在人类基因组中有多个注释替代转录本。几个基本的生物学问题仍未解决:(1) 在肝脏样本和肝细胞系等生物样本中到底存在多少转录本? (2) 在不同条件下,包括在细胞生长和发育过程中、暴露于异生物体(如药物)后,以及在代谢功能障碍相关性脂肪性肝病(MASLD)、酒精相关性肝病(ALD)肝硬化和肥胖症等疾病条件下,不同的 HNF1A-AS1 替代转录本的表达模式是什么?(3) 先前研究中使用的 siRNA 是否会敲除一个或多个转录本?(4) 不同的转录本是否具有相同或不同的基因调控功能?所提供的数据证实了肝脏样本和细胞系中存在几种已注释的 HNF1A-AS1 转录本,同时也发现了一些 Ensembl 基因组数据库中未注释的新转录本。已发现的 HNF1A-AS1 转录本的表达模式与人类胚胎干细胞(hESC)成熟肝细胞样细胞的细胞分化、HepaRG 细胞的生长和分化、利福平诱导反应以及各种肝病状况高度相关。在 HepaRG 生长、分化和对利福平诱导的反应过程中,HNF1A-AS1 转录物的表达水平与细胞色素 P450 酶(如 CYP3A4)的表达水平也高度相关。
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引用次数: 0
Long Non-Coding RNA Levels Are Modulated in Schistosoma mansoni following In Vivo Praziquantel Exposure. 体内接触吡喹酮后曼氏血吸虫体内长非编码 RNA 水平的变化
IF 4.3 Q1 Biochemistry, Genetics and Molecular Biology Pub Date : 2024-04-19 DOI: 10.3390/ncrna10020027
Pedro Jardim Poli, Agatha Fischer-Carvalho, A. Tahira, John D. Chan, S. Verjovski-Almeida, Murilo Sena Amaral
Schistosomiasis is a disease caused by trematodes of the genus Schistosoma that affects over 200 million people worldwide. For decades, praziquantel (PZQ) has been the only available drug to treat the disease. Despite recent discoveries that identified a transient receptor ion channel as the target of PZQ, schistosome response to this drug remains incompletely understood, since effectiveness relies on other factors that may trigger a complex regulation of parasite gene expression. Long non-coding RNAs (lncRNAs) are transcripts longer than 200 nucleotides with low or no protein-coding potential that play important roles in S. mansoni homeostasis, reproduction, and fertility. Here, we show that in vivo PZQ treatment modulates lncRNA levels in S. mansoni. We re-analyzed public RNA-Seq data from mature and immature S. mansoni worms treated in vivo with PZQ and detected hundreds of lncRNAs differentially expressed following drug exposure, many of which are shared among mature and immature worms. Through RT-qPCR, seven out of ten selected lncRNAs were validated as differentially expressed; interestingly, we show that these lncRNAs are not adult worm stage-specific and are co-expressed with PZQ-modulated protein-coding genes. By demonstrating that parasite lncRNA expression levels alter in response to PZQ, this study unravels an important step toward elucidating the complex mechanisms of S. mansoni response to PZQ.
血吸虫病是一种由血吸虫属吸虫引起的疾病,影响着全球 2 亿多人。几十年来,吡喹酮 (PZQ) 一直是治疗这种疾病的唯一药物。尽管最近发现了瞬时受体离子通道是 PZQ 的靶点,但血吸虫对这种药物的反应仍不完全清楚,因为药效取决于其他因素,而这些因素可能会引发寄生虫基因表达的复杂调控。长非编码 RNA(lncRNA)是指长度超过 200 个核苷酸的转录本,其蛋白质编码潜能较低或没有,在曼氏血吸虫的平衡、繁殖和生育中发挥重要作用。在这里,我们发现体内 PZQ 处理可调节曼氏沙门氏菌的 lncRNA 水平。我们重新分析了经 PZQ 体内处理的成熟和未成熟曼森氏杆菌蠕虫的公开 RNA-Seq 数据,检测到数百个 lncRNA 在药物暴露后有差异表达,其中许多在成熟和未成熟蠕虫中共享。有趣的是,我们发现这些lncRNA并不是成虫阶段特异性的,它们与PZQ调控的蛋白编码基因共同表达。通过证明寄生虫 lncRNA 的表达水平会随着对 PZQ 的反应而改变,这项研究为阐明曼氏沙门氏菌对 PZQ 反应的复杂机制迈出了重要的一步。
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引用次数: 0
lncRNA-mRNA Co-Expression and Regulation Analysis in Lung Fibroblasts from Idiopathic Pulmonary Fibrosis. 特发性肺纤维化肺成纤维细胞中 lncRNA-mRNA 的共表达和调控分析
IF 4.3 Q1 Biochemistry, Genetics and Molecular Biology Pub Date : 2024-04-17 DOI: 10.3390/ncrna10020026
Armando López-Martínez, Jovito Cesar Santos-Álvarez, Juan Manuel Velázquez-Enríquez, Alma Aurora Ramírez-Hernández, V. R. Vásquez-Garzón, Rafael Baltiérrez-Hoyos
Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease marked by abnormal accumulation of extracellular matrix (ECM) due to dysregulated expression of various RNAs in pulmonary fibroblasts. This study utilized RNA-seq data meta-analysis to explore the regulatory network of hub long non-coding RNAs (lncRNAs) and messenger RNAs (mRNAs) in IPF fibroblasts. The meta-analysis unveiled 584 differentially expressed mRNAs (DEmRNA) and 75 differentially expressed lncRNAs (DElncRNA) in lung fibroblasts from IPF. Among these, BCL6, EFNB1, EPHB2, FOXO1, FOXO3, GNAI1, IRF4, PIK3R1, and RXRA were identified as hub mRNAs, while AC008708.1, AC091806.1, AL442071.1, FAM111A-DT, and LINC01989 were designated as hub lncRNAs. Functional characterization revealed involvement in TGF-β, PI3K, FOXO, and MAPK signaling pathways. Additionally, this study identified regulatory interactions between sequences of hub mRNAs and lncRNAs. In summary, the findings suggest that AC008708.1, AC091806.1, FAM111A-DT, LINC01989, and AL442071.1 lncRNAs can regulate BCL6, EFNB1, EPHB2, FOXO1, FOXO3, GNAI1, IRF4, PIK3R1, and RXRA mRNAs in fibroblasts bearing IPF and contribute to fibrosis by modulating crucial signaling pathways such as FoxO signaling, chemical carcinogenesis, longevity regulatory pathways, non-small cell lung cancer, and AMPK signaling pathways.
特发性肺纤维化(IPF)是一种进行性肺部疾病,其特征是细胞外基质(ECM)的异常积聚,其原因是肺成纤维细胞中各种 RNA 的表达失调。本研究利用RNA-seq数据荟萃分析来探索IPF成纤维细胞中枢长非编码RNA(lncRNA)和信使RNA(mRNA)的调控网络。荟萃分析揭示了IPF肺成纤维细胞中584个差异表达的mRNA(DEmRNA)和75个差异表达的lncRNA(DElncRNA)。其中,BCL6、EFNB1、EPHB2、FOXO1、FOXO3、GNAI1、IRF4、PIK3R1和RXRA被确定为中枢mRNA,而AC008708.1、AC091806.1、AL442071.1、FAM111A-DT和LINC01989被指定为中枢lncRNA。功能表征显示,这些基因参与了 TGF-β、PI3K、FOXO 和 MAPK 信号通路。此外,这项研究还发现了中枢 mRNA 序列与 lncRNA 之间的调控相互作用。总之,研究结果表明,AC008708.1、AC091806.1、FAM111A-DT、LINC01989 和 AL442071.1 lncRNAs可调控IPF成纤维细胞中的BCL6、EFNB1、EPHB2、FOXO1、FOXO3、GNAI1、IRF4、PIK3R1和RXRA mRNAs,并通过调控FoxO信号、化学致癌、长寿调控通路、非小细胞肺癌和AMPK信号通路等关键信号通路促进纤维化。
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引用次数: 0
miRNAs as Interconnectors between Obesity and Cancer. miRNA 是肥胖症与癌症之间的联系纽带。
IF 4.3 Q1 Biochemistry, Genetics and Molecular Biology Pub Date : 2024-04-15 DOI: 10.3390/ncrna10020024
Grecia Denisse González-Sánchez, A. J. Granados‐López, Y. López-Hernández, Mayra Judith García Robles, Jesús Adrián López
Obesity and cancer are a concern of global interest. It is proven that obesity may trigger the development or progression of some types of cancer; however, the connection by non-coding RNAs has not been totally explored. In the present review, we discuss miRNAs and lncRNAs dysregulation involved in obesity and some cancers, shedding light on how these conditions may exacerbate one another through the dysregulation of ncRNAs. lncRNAs have been reported as regulating microRNAs. An in silico investigation of lncRNA and miRNA interplay is presented. Our investigation revealed 44 upregulated and 49 downregulated lncRNAs in obesity and cancer, respectively. miR-375, miR-494-3p, miR-1908, and miR-196 were found interacting with 1, 4, 4 and 4 lncRNAs, respectively, which are involved in PPARγ cell signaling regulation. Additionally, miR-130 was found to be downregulated in obesity and reported as modulating 5 lncRNAs controlling PPARγ cell signaling. Similarly, miR-128-3p and miR-143 were found to be downregulated in obesity and cancer, interacting with 5 and 4 lncRNAs, respectively, associated with MAPK cell signaling modulation. The delicate balance between miRNA and lncRNA expression emerges as a critical determinant in the development of obesity-associated cancers, presenting these molecules as promising biomarkers. However, additional and deeper studies are needed to reach solid conclusions about obesity and cancer connection by ncRNAs.
肥胖与癌症是全球关注的问题。事实证明,肥胖可能会诱发某些类型癌症的发生或发展;然而,非编码 RNA 与癌症之间的联系尚未得到全面探讨。在本综述中,我们讨论了肥胖和某些癌症所涉及的 miRNAs 和 lncRNAs 的失调,揭示了这些病症如何通过 ncRNAs 的失调而相互加重。本文介绍了对 lncRNA 和 miRNA 相互作用的硅学研究。我们的研究发现,在肥胖症和癌症中,分别有 44 个 lncRNA 上调和 49 个 lncRNA 下调,其中 miR-375、miR-494-3p、miR-1908 和 miR-196 分别与 1、4、4 和 4 个 lncRNA 相互作用,这些 lncRNA 参与 PPARγ 细胞信号的调控。此外,研究还发现,miR-130 在肥胖症中下调,并报道它调节了 5 个控制 PPARγ 细胞信号传导的 lncRNA。同样,miR-128-3p 和 miR-143 在肥胖症和癌症中被下调,分别与 5 个和 4 个与 MAPK 细胞信号调节相关的 lncRNA 相互作用。miRNA和lncRNA表达之间的微妙平衡成为肥胖相关癌症发展的关键决定因素,使这些分子成为有前景的生物标志物。然而,要想通过 ncRNA 就肥胖与癌症的关系得出可靠的结论,还需要更多更深入的研究。
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引用次数: 0
Possible Involvement of Long Non-Coding RNAs GNAS-AS1 and MIR205HG in the Modulation of 5-Fluorouracil Chemosensitivity in Colon Cancer Cells through Increased Extracellular Release of Exosomes. 长非编码 RNA GNAS-AS1 和 MIR205HG 可能通过增加细胞外释放外泌体参与调节结肠癌细胞对 5 氟尿嘧啶的化疗敏感性
IF 4.3 Q1 Biochemistry, Genetics and Molecular Biology Pub Date : 2024-04-15 DOI: 10.3390/ncrna10020025
S. Azwar, C. T. Ng, S. Y. Zahari Sham, H. F. Seow, Minhian Chai, Mohd Faizal Ghazali, M. F. Jabar
A growing number of studies have suggested the involvement of long non-coding RNAs as the key players in not just the initiation and progression of the tumor microenvironment, but also in chemotherapy tolerance. In the present study, generated 5-FU-resistant SW480/DR cells were analyzed via cDNA microarray for its aberrant lncRNAs and mRNAs expression in comparison with the 5-FU-susceptible SW480/DS cells. Among the 126 lncRNAs described, lncRNAs GNAS-AS1, MIR205HG, and LOC102723721 have been identified to be significantly upregulated, while lncRNs lnc-RP11-597K23.2.1-2, LOC100507639, and CCDC144NL-AS1 have been found to be significantly downregulated. In the meantime, bioinformatic analysis through gene ontology studies of aberrantly expressed mRNAs revealed "regulated exocytosis", among others, as the biological process most impacted in SW480/DR cells. To investigate, exosome purification was then carried out and its characterization were validated via transmission electron microscopy and nanoparticle tracking analysis. Interestingly, it was determined that the 5-FU-resistant SW480/DR cells secretes significantly higher concentration of extracellular vesicles, particularly, exosomes when compared to the 5-FU-susceptible SW480/DS cells. Based on the lncRNA-mRNA interaction network analysis generated, lncRNA GNAS-AS1 and MIR205HG have been identified to be potentially involved in the incidence of 5-FU resistance in SW480 colon cancer cells through promoting increased release of exosomes into the intercellular matrix. Our study hopes not only to provide insights on the list of involved candidate lncRNAs, but also to elucidate the role exosomes play in the initiation and development of 5-FU chemotherapy resistance in colon cancer cells.
越来越多的研究表明,长非编码RNA不仅是肿瘤微环境发生和发展的关键因素,也是化疗耐受性的关键因素。本研究通过 cDNA 微阵列分析了生成的 5-FU 耐药 SW480/DR 细胞与 5-FU 易感 SW480/DS 细胞的异常 lncRNAs 和 mRNAs 表达。在所描述的126个lncRNA中,发现lncRNA GNAS-AS1、MIR205HG和LOC102723721被显著上调,而lncRN lnc-RP11-597K23.2.1-2、LOC100507639和CCDC144NL-AS1被显著下调。与此同时,通过对异常表达的 mRNA 进行基因本体论研究进行生物信息学分析,发现 "调控外泌 "等是在 SW480/DR 细胞中受影响最大的生物过程。研究人员随后进行了外泌体纯化,并通过透射电子显微镜和纳米粒子追踪分析验证了其特征。有趣的是,与对5-FU敏感的SW480/DS细胞相比,对5-FU耐药的SW480/DR细胞分泌的胞外囊泡浓度明显更高,尤其是外泌体。根据所生成的lncRNA-mRNA相互作用网络分析,发现lncRNA GNAS-AS1和MIR205HG可能通过促进外泌体向细胞间质的释放而参与了SW480结肠癌细胞5-FU耐药性的发生。我们的研究不仅希望提供有关候选lncRNA的见解,还希望阐明外泌体在结肠癌细胞5-FU化疗耐药性的产生和发展过程中所起的作用。
{"title":"Possible Involvement of Long Non-Coding RNAs GNAS-AS1 and MIR205HG in the Modulation of 5-Fluorouracil Chemosensitivity in Colon Cancer Cells through Increased Extracellular Release of Exosomes.","authors":"S. Azwar, C. T. Ng, S. Y. Zahari Sham, H. F. Seow, Minhian Chai, Mohd Faizal Ghazali, M. F. Jabar","doi":"10.3390/ncrna10020025","DOIUrl":"https://doi.org/10.3390/ncrna10020025","url":null,"abstract":"A growing number of studies have suggested the involvement of long non-coding RNAs as the key players in not just the initiation and progression of the tumor microenvironment, but also in chemotherapy tolerance. In the present study, generated 5-FU-resistant SW480/DR cells were analyzed via cDNA microarray for its aberrant lncRNAs and mRNAs expression in comparison with the 5-FU-susceptible SW480/DS cells. Among the 126 lncRNAs described, lncRNAs GNAS-AS1, MIR205HG, and LOC102723721 have been identified to be significantly upregulated, while lncRNs lnc-RP11-597K23.2.1-2, LOC100507639, and CCDC144NL-AS1 have been found to be significantly downregulated. In the meantime, bioinformatic analysis through gene ontology studies of aberrantly expressed mRNAs revealed \"regulated exocytosis\", among others, as the biological process most impacted in SW480/DR cells. To investigate, exosome purification was then carried out and its characterization were validated via transmission electron microscopy and nanoparticle tracking analysis. Interestingly, it was determined that the 5-FU-resistant SW480/DR cells secretes significantly higher concentration of extracellular vesicles, particularly, exosomes when compared to the 5-FU-susceptible SW480/DS cells. Based on the lncRNA-mRNA interaction network analysis generated, lncRNA GNAS-AS1 and MIR205HG have been identified to be potentially involved in the incidence of 5-FU resistance in SW480 colon cancer cells through promoting increased release of exosomes into the intercellular matrix. Our study hopes not only to provide insights on the list of involved candidate lncRNAs, but also to elucidate the role exosomes play in the initiation and development of 5-FU chemotherapy resistance in colon cancer cells.","PeriodicalId":19271,"journal":{"name":"Non-Coding RNA","volume":null,"pages":null},"PeriodicalIF":4.3,"publicationDate":"2024-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140702893","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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Non-Coding RNA
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