competing endogenous RNAs

竞争的内源性 RNA
  • 文章类型: Journal Article
    癌症干细胞(CSC)是导致癌症异质性的细胞类型之一。癌细胞停滞在G0,并通过自我更新和多能性产生非CSC后代,导致肿瘤复发,转移,对化疗有抵抗力.它们可以刺激肿瘤复发并重新生长转移性肿瘤。所以,CSC是根除肿瘤的有希望的靶标,并且已经考虑开发抗CSC疗法。近年来,竞争性内源性RNA(ceRNA)已成为一类重要的转录后调节因子,通过竞争microRNA(miRNA)结合来影响基因表达。此外,ceRNA的异常表达与肿瘤进展有关。最近的发现表明,ceRNA网络可以通过对CSC的作用引起肿瘤进展。为了克服因CSC而产生的治疗抗性,我们需要提高目前对ceRNAs参与CSC相关复发的机制的认识.因此,这篇综述旨在讨论ceRNAs在CSCs功能中的作用。靶向ceRNAs可能为新的癌症治疗靶点开辟道路,并可用于临床研究。
    Cancer stem cells (CSCs) are one of the cell types that account for cancer heterogeneity. The cancer cells arrest in G0 and generate non-CSC progeny through self-renewal and pluripotency, resulting in tumor recurrence, metastasis, and resistance to chemotherapy. They can stimulate tumor relapse and re-grow a metastatic tumor. So, CSCs is a promising target for eradicating tumors, and developing an anti-CSCs therapy has been considered. In recent years competing endogenous RNA (ceRNA) has emerged as a significant class of post-transcriptional regulators that affect gene expression via competition for microRNA (miRNA) binding. Furthermore, aberrant ceRNA expression is associated with tumor progression. Recent findings show that ceRNA network can cause tumor progression through the effect on CSCs. To overcome therapeutic resistance due to CSCs, we need to improve our current understanding of the mechanisms by which ceRNAs are implicated in CSC-related relapse. Thus, this review was designed to discuss the role of ceRNAs in CSCs\' function. Targeting ceRNAs may open the path for new cancer therapeutic targets and can be used in clinical research.
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  • 文章类型: Journal Article
    系统性红斑狼疮(SLE)是一种以免疫炎症和多器官损伤为特征的疾病。最近的研究已经将竞争性内源性RNA(ceRNA)与狼疮联系起来。然而,ceRNAs网络影响SLE的确切机制尚不清楚。本研究旨在探讨ceRNAs网络的调控功能,是控制SLE病理生理过程的重要途径。
    用于我们测试的测定的CircRNA微阵列来自我们医院的三个健康个体和三个SLE患者的骨髓样本。circRNA的其他测序数据,miRNA和mRNA从基因表达综合(GEO)数据集获得。使用R程序的limma包,在GEO数据库中发现mRNA和miRNA的差异表达。然后使用miRMap建立预测的miRNA-mRNA和circRNA-miRNA,miRanda,miRDB,TargetScan,还有mitarBase.使用CytoscRNA构建CircRNA-miRNA-mRNAceRNA网络,和hub基因使用蛋白质-蛋白质相互作用网络进行筛选。中枢基因的免疫浸润分析也由CIBERSORT和GSEA进行。
    230个重叠的circRNAs,与健康对照相比,在SLE患者中鉴定了86个DEmiRNA和2083个DEmRNA。我们构建了一个circRNA-miRNA-mRNAceRNAs网络,包含11个重叠的circRNAs,9个miRNA和51个mRNA。ESR1和SIRT1是PPI网络中最常见的相关蛋白质-蛋白质相互作用。KEGG分析显示,DEGs在FoxO信号通路以及脂质和动脉粥样硬化中富集。我们构建了一个新的circRNA-miRNA-mRNAceRNA网络(HSAcirc0000345-HSAmiR-22-3-P-ESR1/SIRT1),可能对SLE产生重大影响。
    通过这种生物信息学和综合分析,我们建议ceRNA网络在SLE的发病机制和治疗中的调节作用。
    UNASSIGNED: Systemic lupus erythematosus (SLE) is a disease characterised by immune inflammation and damage to multiple organs. Recent investigations have linked competing endogenous RNAs (ceRNAs) to lupus. However, the exact mechanism through which the ceRNAs network affects SLE is still unclear. This study aims to investigate the regulatory functions of the ceRNAs network, which are important pathways that control the pathophysiological processes of SLE.
    UNASSIGNED: CircRNA microarray for our tested assays were derived from bone marrow samples from three healthy individuals and three SLE patients in our hospital. The other sequencing data of circRNA, miRNA and mRNA were obtained from Gene Expression Omnibus (GEO) datasets. Using the limma package of R program, the differential expression of mRNA and miRNA in the GEO database was discovered. Then predicted miRNA-mRNA and circRNA-miRNA were established using miRMap, miRanda, miRDB, TargetScan, and miTarBase. CircRNA-miRNA-mRNA ceRNA network was constructed using Cytoscape, and hub genes were screened using a protein-protein interaction network. Immune infiltration analysis of the hub gene was also performed by CIBERSORT and GSEA.
    UNASSIGNED: 230 overlapped circRNAs, 86 DEmiRNAs and 2083 DEmRNAs were identified in SLE patients as compared to healthy controls. We constructed a circRNA-miRNA-mRNA ceRNAs network contained 11 overlapped circRNAs, 9 miRNAs and 51 mRNAs. ESR1 and SIRT1 were the most frequently associated protein-protein interactions in the PPI network. KEGG analysis showed that DEGs was enriched in FoxO signaling pathway as well as lipids and atherosclerosis. We constructed a novel circRNA-miRNA-mRNA ceRNA network (HSA circ 0000345- HSA miR-22-3-P-ESR1/SIRT1) that may have a major impact on SLE.
    UNASSIGNED: Through this bioinformatics and integrated analysis, we suggest a regulatory role for ceRNA network in the pathogenesis and treatment of SLE.
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  • 文章类型: Journal Article
    目的:本研究旨在研究大麻二酚(CBD)对甲基苯丙胺(METH)诱导的雄性小鼠复发和行为敏化的药理作用及其潜在机制。
    方法:使用具有偏倚范式和开放场测试的条件位置偏好(CPP)测试来评估CBD对METH诱导的雄性小鼠复发和行为敏化的影响。RNA测序和生物信息学分析用于鉴定差异表达(DE)circRNAs,miRNA,和小鼠伏隔核(NAc)中的mRNA,并使用竞争性内源RNA(ceRNA)网络分析预测它们之间的相互作用。
    结果:在METH戒断期长期施用CBD(40mg/kg)减轻了METH(2mg/kg)诱导的小鼠CPP恢复和行为敏化,以及行为敏感后的情绪和认知障碍。此外,42DEcircRNAs,11个DEmiRNA,在小鼠的NAc中鉴定出40个DEmRNA。小鼠NAc中的circMeis2-miR-183-5p-Kcnj5网络涉及CBD对METH诱导的CPP恢复和行为敏化的影响。
    结论:本研究首次构建了ceRNAs网络,揭示CBD治疗METH诱导的CPP恢复和行为敏化的潜在机制,从而推进CBD在METH使用障碍中的应用。
    This study aims to investigate the pharmacological effects and the underlying mechanism of cannabidiol (CBD) on methamphetamine (METH)-induced relapse and behavioral sensitization in male mice.
    The conditioned place preference (CPP) test with a biased paradigm and open-field test were used to assess the effects of CBD on METH-induced relapse and behavioral sensitization in male mice. RNA sequencing and bioinformatics analysis was employed to identify differential expressed (DE) circRNAs, miRNAs, and mRNAs in the nucleus accumbens (NAc) of mice, and the interaction among them was predicted using competing endogenous RNAs (ceRNAs) network analysis.
    Chronic administration of CBD (40 mg/kg) during the METH withdrawal phase alleviated METH (2 mg/kg)-induced CPP reinstatement and behavioral sensitization in mice, as well as mood and cognitive impairments following behavioral sensitization. Furthermore, 42 DEcircRNAs, 11 DEmiRNAs, and 40 DEmRNAs were identified in the NAc of mice. The circMeis2-miR-183-5p-Kcnj5 network in the NAc of mice is involved in the effects of CBD on METH-induced CPP reinstatement and behavioral sensitization.
    This study constructed the ceRNAs network for the first time, revealing the potential mechanism of CBD in treating METH-induced CPP reinstatement and behavioral sensitization, thus advancing the application of CBD in METH use disorders.
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  • 文章类型: Journal Article
    竞争的内源性RNA通过转录后相互作用中的串扰在细胞分子机制中发挥关键作用。关于ceRNA串扰的研究,这尤其取决于大量的自由转录本,通常涉及大规模和小规模研究,涉及整合来自组织和相关性分析的转录组数据。ceRNA相互作用的这种丰度依赖性表明组织和条件特异性ceRNA动力学可能会波动。然而,没有全面的研究调查正常组织中的ceRNA相互作用,在癌组织或其相互作用中丢失和/或出现的ceRNA。在这项研究中,我们全面分析了在三种发病率最高的癌症中观察到的肿瘤特异性ceRNA波动,LUAD,PRAD,和BRCA,与健康的肺相比,前列腺,和乳房组织,分别。我们对肿瘤特异性竞争性内源性RNA(ceRNA)相互作用的观察表明,在肺腺癌(LUAD)的情况下,前列腺腺癌(PRAD),和乳腺浸润性癌(BRCA),3,204,1,233和406个CERNA,分别,参与肿瘤组织内的转录后通讯,与它们在相应健康样本中的缺失相反。我们还发现,三种癌症类型共有90个ceRNA,与正常组织相比,这些ceRNA参与肿瘤组织中的ceRNA相互作用。在与miRNAs直接相互作用的90个ceRNAs中,我们发现了一个由165个miRNAs和63个ceRNAs组成的核心网络,这些核心网络在未来的研究中应该被考虑用于RNA靶向和RNA介导的方法,并且可以用于这三种侵袭性癌症类型.更具体地说,在这个核心互动网络中,ceRNAs如GALNT7、KLF9和DAB2,miRNAs如miR-106a/b-5p,miR-20a-5p,miR-519d-3p可能作为三种关键癌症的共同靶标。与使用与正常组织相比的差异表达基因构建ceRNA网络的常规方法相反,我们提出的方法通过考虑ceRNA:miRNA相互作用中的上下文来识别ceRNA参与者。我们的结果有可能揭示癌症类型中独特和常见的ceRNA相互作用,并确定关键RNA。从而为对抗癌症的基于RNA的策略铺平了道路。
    Competing endogenous RNAs play key roles in cellular molecular mechanisms through cross-talk in post-transcriptional interactions. Studies on ceRNA cross-talk, which is particularly dependent on the abundance of free transcripts, generally involve large- and small-scale studies involving the integration of transcriptomic data from tissues and correlation analyses. This abundance-dependent nature of ceRNA interactions suggests that tissue- and condition-specific ceRNA dynamics may fluctuate. However, there are no comprehensive studies investigating the ceRNA interactions in normal tissue, ceRNAs that are lost and/or appear in cancerous tissues or their interactions. In this study, we comprehensively analyzed the tumor-specific ceRNA fluctuations observed in the three highest-incidence cancers, LUAD, PRAD, and BRCA, compared to healthy lung, prostate, and breast tissues, respectively. Our observations pertaining to tumor-specific competing endogenous RNA (ceRNA) interactions revealed that, in the cases of lung adenocarcinoma (LUAD), prostate adenocarcinoma (PRAD), and breast invasive carcinoma (BRCA), 3,204, 1,233, and 406 ceRNAs, respectively, engage in post-transcriptional intercommunication within tumor tissues, in contrast to their absence in corresponding healthy samples. We also found that 90 ceRNAs are shared by the three cancer types and that these ceRNAs participate in ceRNA interactions in tumor tissues compared to those in normal tissues. Among the 90 ceRNAs that directly interact with miRNAs, we uncovered a core network of 165 miRNAs and 63 ceRNAs that should be considered in RNA-targeted and RNA-mediated approaches in future studies and could be used in these three aggressive cancer types. More specifically, in this core interaction network, ceRNAs such as GALNT7, KLF9, and DAB2 and miRNAs like miR-106a/b-5p, miR-20a-5p, and miR-519d-3p may have potential as common targets in the three critical cancers. In contrast to conventional methods that construct ceRNA networks using differentially expressed genes compared to normal tissues, our proposed approach identifies ceRNA players by considering their context within the ceRNA:miRNA interactions. Our results have the potential to reveal distinct and common ceRNA interactions in cancer types and to pinpoint critical RNAs, thereby paving the way for RNA-based strategies in the battle against cancer.
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  • 文章类型: Journal Article
    非生物/生物胁迫通过影响植物生长对农业和粮食安全构成重大威胁。生产力和质量。不编码蛋白质的大RNA转录物的广泛转录的发现,称为长非编码RNA(lncRNAs),长度大于200个核苷酸,为RNA在基因调控中的中心地位提供了一个重要的新视角。在植物中,lncRNAs广泛存在并在应激反应中实现多种生物学功能。在本文中,综述了lncRNA在植物逆境响应中的生物学功能研究进展,如自然反义转录本(NAT),竞争内源性RNA(ceRNA)和染色质修饰等。在植物中,lncRNAs作为几个植物激素途径的关键调控中心,整合脱落酸(ABA),茉莉酸(JA),水杨酸(SA)和氧化还原信号对许多非生物/生物胁迫的反应。此外,在应激反应性lncRNAs中富集的保守序列基序和结构基序也可能负责lncRNAs的应激反应功能,它将为lncRNA研究提供新的焦点和策略。一起来看,我们强调了lncRNAs在整合植物对不利环境条件的反应与植物生长和发育的不同方面的独特作用。我们设想,对lncRNAs调节植物应激反应的机制的更好理解可能进一步促进培育抗逆作物的非常规方法的发展。
    Abiotic/biotic stresses pose a major threat to agriculture and food security by impacting plant growth, productivity and quality. The discovery of extensive transcription of large RNA transcripts that do not code for proteins, termed long non-coding RNAs (lncRNAs) with sizes larger than 200 nucleotides in length, provides an important new perspective on the centrality of RNA in gene regulation. In plants, lncRNAs are widespread and fulfill multiple biological functions in stress response. In this paper, the research advances on the biological function of lncRNA in plant stress response were summarized, like as Natural Antisense Transcripts (NATs), Competing Endogenous RNAs (ceRNAs) and Chromatin Modification etc. And in plants, lncRNAs act as a key regulatory hub of several phytohormone pathways, integrating abscisic acid (ABA), jasmonate (JA), salicylic acid (SA) and redox signaling in response to many abiotic/biotic stresses. Moreover, conserved sequence motifs and structural motifs enriched within stress-responsive lncRNAs may also be responsible for the stress-responsive functions of lncRNAs, it will provide a new focus and strategy for lncRNA research. Taken together, we highlight the unique role of lncRNAs in integrating plant response to adverse environmental conditions with different aspects of plant growth and development. We envisage that an improved understanding of the mechanisms by which lncRNAs regulate plant stress response may further promote the development of unconventional approaches for breeding stress-resistant crops.
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  • 文章类型: Journal Article
    越来越多的证据表明,竞争性内源性RNA(ceRNA)网络的破坏在骨肉瘤(OS)的发生和发展中起着重要作用。然而,ceRNAs在OS中的具体作用和功能尚不清楚.首先,通过挖掘E-MTAB-1136和GSE28423数据集来鉴定差异表达的微小RNA(DEM)。使用MiRWalk网站预测miRNA的靶基因。从公开的微阵列数据库下载OS相关环状RNA(circRNA)表达谱。通过逆转录-定量PCR和蛋白质印迹评估基因表达水平。使用CellCountingKit-8,Transwell研究了circKEAP1,microRNA(miR)-486-3p和膜相关RINGCH指蛋白1(MARCH1)在OS细胞中的生物学效应,集落形成和伤口愈合测定。miR-486-3p在OS组织和细胞系中异常下调,并充满外泌体。显示miR-486-3p过表达在体外抑制OS细胞进展并促进细胞周期停滞。此外,MARCH1在OS细胞中被鉴定为miR-486-3p的直接下游分子。发现circKEAP1在OS组织和细胞中上调。发现circKEAP1具有与miR-486-3p的结合位点。机械上,circKEAP1通过海绵作用miR-486-3p正调节MARCH1表达。外泌体miR-486-3p通过形成circKEAP1/MARCH1轴抑制OS的进展。这些发现可能为OS提供一种有希望的治疗方法。
    Accumulating evidence shows that the disruption of competing endogenous RNA (ceRNA) networks plays a significant role in osteosarcoma (OS) initiation and progression. However, the specific roles and functions of the ceRNAs in OS remain unclear. First, differentially expressed microRNAs (DEMs) were identified by mining the E-MTAB-1136 and GSE28423 datasets. MiRWalk website was used to predict the target gene of miRNA. OS-associated circular RNA (circRNA) expression profiles were downloaded from the published microarray databases. Gene expression levels were assessed through reverse transcription-quantitative PCR and western blotting. The biological effects of circKEAP1, microRNA (miR)-486-3p and membrane-associated RINGCH finger protein 1 (MARCH1) in OS cells were investigated using Cell Counting Kit-8, Transwell, colony formation and wound healing assays. miR-486-3p was aberrantly downregulated in OS tissues and cell lines and was packed with exosomes. miR-486-3p overexpression was shown to inhibit OS cell progression and promoted cell cycle arrest in vitro. In addition, MARCH1 was identified as a direct downstream molecule of miR-486-3p in OS cells. circKEAP1 was found to be upregulated in OS tissues and cells. circKEAP1 was found to have binding sites with miR-486-3p. Mechanistically, circKEAP1 positively regulated MARCH1 expression by sponging miR-486-3p. Exosomal miR-486-3p inhibited the progression of OS by sponging the circKEAP1/MARCH1 axis. These findings may provide a promising treatment approach for OS.
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  • 文章类型: Journal Article
    雌性鲤鱼比雄性个体生长更快,暗示饲养雌性在水产养殖中可能更有利可图。非编码RNA(ncRNAs)作为多功能调节因子,在不同的生物过程中具有多种功能。然而,ncRNAs在鲤鱼性别分化中的作用研究较少。在这项研究中,我们研究了ncRNAs的表达谱,包括miRNAs,lncRNAs,和circRNAs,了解ncRNAs在鲤鱼性别分化中的作用。在卵巢和睾丸中鉴定了大量的差异表达(DE)ncRNA。一些miRNA,特别是miR-205、miR-214和miR-460-5p,可能调节激素合成,从而维持性生活。一种新的miRNA,new_158,预测会抑制foxl3的表达。DElncRNAs与卵母细胞减数分裂相关,GnRH信号通路,和类固醇的生物合成,而DEcircRNA靶基因富集在WNT信号通路和MAPK信号通路。我们还分析了ncRNA-mRNA相互作用,以揭示竞争内源性RNA(ceRNA)之间的串扰,这是lncRNAs和circRNAs发挥作用的关键机制。一些lncRNAs和circRNAs可能能够竞争性地结合new_313,一种新的miRNA,从而调节hsd17β3。我们的研究将为了解鲤鱼性腺分化和发育的遗传基础提供宝贵的资源。
    Female common carp grow faster than male individuals, implying that rearing females could be more profitable in aquaculture. Non-coding RNAs (ncRNAs) serve as versatile regulators with multiple functions in diverse biological processes. However, the roles of ncRNAs in the sex differentiation of common carp are less studied. In this study, we investigated the expression profiles of ncRNAs, including miRNAs, lncRNAs, and circRNAs, in the gonads to comprehend the roles of ncRNAs in sex differentiation in common carp. A substantial number of differentially expressed (DE) ncRNAs in ovaries and testes were identified. Some miRNAs, notably miR-205, miR-214, and miR-460-5p, might modulate hormone synthesis and thus maintain sex. A novel miRNA, novel_158, was predicted to suppress the expression of foxl3. DE lncRNAs were associated with oocyte meiosis, GnRH signaling pathways, and steroid biosynthesis, while DE circRNA target genes were enriched in the WNT signaling pathway and MAPK signaling pathway. We also analyzed ncRNA-mRNA interactions to shed light on the crosstalk between competing endogenous RNAs (ceRNAs), which is the critical mechanism by which lncRNAs and circRNAs function. Some lncRNAs and circRNAs may be able to competitively bind novel_313, a new miRNA, and thus regulate hsd17β3. Our research will provide a valuable resource for understanding the genetic basis of gonadal differentiation and development in common carp.
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  • 文章类型: Journal Article
    竞争性内源性RNA(ceRNA)和肿瘤浸润免疫细胞在结直肠癌(CRC)肿瘤发生中起着至关重要的作用。然而,其在老年CRC患者中的预后作用尚不清楚.从癌症基因组图谱下载老年CRC患者的基因表达谱和临床信息。单变量,拉索,和多变量Cox回归分析用于筛选关键ceRNA并防止过拟合。共纳入265例老年CRC患者。我们构建了一个由17个lncRNAs组成的新型ceRNA网络,35个miRNAs,和5个mRNA。我们基于四个关键的ceRNA(ceRNA列线图)建立了三个预后预测列线图,五个关键免疫细胞(免疫细胞列线图),和它们的组合(ceRNA-免疫细胞列线图)。其中,ceRNA免疫细胞列线图的准确性最好。此外,ceRNA-免疫细胞列线图的曲线下面积也显著大于1时的TNM分期(0.818vs.0.693),3(0.865vs.0.674),和5(0.832vs.0.627)年。共表达分析显示CBX6与活化的树突状细胞呈正相关(R=0.45,p<0.01),而与激活的肥大细胞呈负相关(R=-0.43,p<0.01)。总之,我们的研究构建了三个列线图来预测老年CRC患者的预后,其中,ceRNA-免疫细胞列线图具有最好的预测准确性。我们推测,CBX6对活化的树突状细胞和肥大细胞的调节机制可能在老年CRC患者的肿瘤发展和预后中起着至关重要的作用。
    Competitive endogenous RNAs (ceRNAs) and tumor-infiltrating immune cells play essential roles in colorectal cancer (CRC) tumorigenesis. However, their prognostic role in elderly patients with CRC is unclear. Gene expression profiles and clinical information for elderly patients with CRC were downloaded from The Cancer Genome Atlas. Univariate, LASSO, and multivariate Cox regression analyses were utilized for screening key ceRNAs and prevent overfitting. A total of 265 elderly patients with CRC were included. We constructed a novel ceRNA network consisting of 17 lncRNAs, 35 miRNAs, and 5 mRNAs. We established three prognosis predictive nomograms based on four key ceRNAs (ceRNA nomogram), five key immune cells (immune cell nomogram), and their combination (ceRNA-immune cell nomogram). Among them, the ceRNA-immune cell nomogram had the best accuracy. Furthermore, the areas under the curve of the ceRNA-immune cell nomogram were also significantly greater than the TNM stage at 1 (0.818 vs. 0.693), 3 (0.865 vs. 0.674), and 5 (0.832 vs. 0.627) years. Co-expression analysis revealed that CBX6 was positively correlated with activated dendritic cells (R = 0.45, p < 0.01), whereas negatively correlated with activated mast cells (R =- 0.43, p < 0.01). In conclusion, our study constructed three nomograms to predict prognosis in elderly patients with CRC, among which the ceRNA-immune cell nomogram had the best prediction accuracy. We inferred that the mechanism underlying the regulation of activated dendritic cells and mast cells by CBX6 might play a crucial role in tumor development and prognosis of elderly patients with CRC.
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  • 文章类型: Journal Article
    绒山羊毛囊分为初级毛囊和次级毛囊。初级毛囊产生粗糙的头发,次级毛囊产生羊绒。毛囊的发育受多种信号分子和途径的影响。研究表明,非编码RNA广泛参与山羊毛囊的发育,包括小RNA(miRNA),长链非编码RNA(lncRNA),和环状RNAs(circRNAs)。近年来,circRNAs,作为一种新型的环状封闭非编码RNA,由于它们的高稳定性而引起了极大的关注。然而,其对绒山羊毛囊的调节作用主要集中在次级毛囊的周期性调控上,没有关于胎儿期绒山羊毛囊发育的报道。因此,这项研究是基于circRNA,miRNA,对内蒙古绒山羊胎儿期(第45、55、65、75天)皮肤组织进行全转录测序,筛选出不同时期毛囊形态变化,得到mRNA表达谱。总共存在113个与次级毛囊发育有关的circRNAs。根据ceRNA调控网络的原理,由13个circRNAs组成的ceRNA调控网络,21个miRNAs,构建了110个与次级毛囊发育有关的mRNA。然后,qRT-PCR和Sanger测序鉴定circRNA2034、circRNA5712、circRNA888和circRNA9127是circRNAs。接下来,双荧光素酶报告基因验证了circRNA5712-miR-27b-3p-Dll4的靶向关系。总之,本研究构建了绒山羊次级毛囊发育的ceRNA调控网络,为分析circRNAs通过ceRNA机制调控绒山羊次级毛囊的形态发生和发育奠定基础。
    Cashmere goat hair follicles are divided into primary hair follicles and secondary hair follicles. The primary hair follicles produce coarse hair, and the secondary hair follicles produce cashmere. The development of hair follicles is affected by a variety of signaling molecules and pathways. Studies have shown that non-coding RNAs are widely involved in the development of hair follicles of the goat, including small RNAs (miRNAs), long non-coding RNAs (lncRNA), and circular RNAs (circRNAs). In recent years, circRNAs, as a new type of circular closed non-coding RNAs, have attracted great attention due to their high stability. However, its regulatory effect on cashmere goat hair follicles mainly focuses on the periodic regulation of secondary hair follicles, and there is no report on the development of cashmere goat hair follicles during the fetal period. Therefore, this study was based on the circRNA, miRNA, and mRNA expression profiles obtained by whole-transcriptional sequencing of the skin tissue of the Inner Mongolia cashmere goats in the fetal period (days 45, 55, 65, and 75) and screening out the morphological changes of hair follicles at different periods. A total of 113 circRNAs related to the development of secondary hair follicles were present. According to the principle of the ceRNA regulatory network, a ceRNA regulatory network composed of 13 circRNAs, 21 miRNAs, and 110 mRNAs related to the development of secondary hair follicles was constructed. Then, qRT-PCR and Sanger sequencing identified circRNA2034, circRNA5712, circRNA888, and circRNA9127 were circRNAs. Next, the dual-luciferase reporter gene verified the targeting relationship of circRNA5712-miR-27b-3p-Dll4. In conclusion, this study constructed a ceRNA regulatory network for the development of cashmere goat secondary hair follicles, laying a foundation for the analysis of circRNAs regulating the morphogenesis and development of cashmere goat secondary hair follicles through the ceRNA mechanism.
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  • 文章类型: Journal Article
    研究表明,蛋氨酸限制(MR)可以抑制肿瘤的进展,但其在结肠癌中的作用机制尚不清楚。通过对GSE72131和GSE103602数据集的DESeq2和Edge分析,鉴定了受MR影响的649个共同上调和532个共同下调的基因,分别。富集分析显示这些基因与肿瘤进展密切相关。结合癌症基因组图谱数据库中结肠癌的差异表达基因,MR影响结肠癌中330个失调的基因。在此基础上,建立了转录调控和竞争的内源性RNA网络,并将F转录因子1和microRNA17-92a-1簇宿主基因鉴定为关键转录因子和长链非编码RNA,分别。此外,四个基因(FA互补组I,Holliday连接识别蛋白,通过分析失调基因与总体生存率之间的关系,鉴定了核蛋白亚基Alpha2和Kinesin家族成员15)。最后,西方印迹,逆转录-定量PCR,Transwell等体外实验证实MR抑制HCT116结肠癌细胞增殖,转移和侵袭,诱导细胞凋亡并下调6个hub基因。总的来说,本研究确定了MR抑制结肠癌进展的潜在靶标,并有助于MR的临床应用。
    Studies have shown that methionine restriction (MR) can inhibit tumor progression, but its mechanism in colon cancer is unknown. Through DESeq2 and Edge analysis of the GSE72131 and GSE103602 datasets, 649 co-upregulated and 532 co-downregulated genes affected by MR were identified, respectively. Enrichment analysis showed that these genes were closely associated with tumor progression. Combined with the differentially expressed genes of colon cancer in The Cancer Genome Atlas database, MR affected 330 dysregulated genes in colon cancer. On this basis, a transcriptional regulatory and competing endogenous RNA network was established and F transcription factor 1 and microRNA 17-92a-1 Cluster Host Gene were identified as a key transcription factor and long non-coding RNA, respectively. In addition, four genes (FA Complementation Group I, Holliday Junction Recognition Protein, Karyopherin Subunit Alpha 2 and Kinesin Family Member 15) were identified by analyzing the relationship between dysregulated genes and overall survival. Finally, western blotting, reverse transcription-quantitative PCR, Transwell and other in vitro experiments verified that MR inhibits HCT116 colon cancer cell proliferation, metastasis and invasion, induces apoptosis and downregulates 6 hub genes. Collectively, the present study identified potential targets for MR to inhibit colon cancer progression and contributed to the clinical application of MR.
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