RNA, Circular

RNA, 环状
  • 文章类型: Journal Article
    腹主动脉瘤(AAA)是严重威胁人类健康并带来巨大经济负担的心血管疾病。目前,其发病机制尚不清楚,其治疗仅限于手术治疗。随着对铁死亡机制研究的深入和分析,为AAA患者的临床管理提供了新的思路,包括诊断,治疗和预防。因此,本文旨在构建基于铁凋亡的竞争性内源性RNA(ceRNA)调控轴,以初步探索AAA的发病机制和潜在治疗靶点。我们从GSE144431数据集和60个已知的铁凋亡相关基因获得了上调和下调的铁凋亡相关DEGs(FRGs)。采用Pearson相关分析在AAA样品中找到醛酮还原酶1C(AKR1C1)。通过基因本体论(GO)和京都基因和基因组百科全书(KEGG)进行这些基因的富集分析。通过单样本基因集富集分析(ssGSEA)研究免疫细胞与AKR1C1的相关性。通过TargetScan数据库和miRWalk数据库预测AKR1C1-miRNA对。通过CircInteractome数据库选择环状RNA(CircRNA)-miRNA对。通过维恩图可视化circRNA-miRNA和AKR1C1-miRNA对之间的重叠miRNA。最后,通过搜索重叠miRNA的上游circRNA和下游mRNA,构建circRNA-miRNA-mRNA轴.在GSE144431和60个铁凋亡相关基因中仅发现一个下调的AKR1C1基因。进一步探索AKR1C1相关基因的功能富集和通路分析,据观察,它们主要富含对氧化应激的反应,\"\"谷胱甘肽生物合成过程\"和\"非核糖体肽生物合成过程,\"\"Ferroptosis,\"\"谷胱甘肽代谢\"和\"化学致癌作用-活性氧。“还发现它们与大多数免疫细胞显着相关,包括激活的树突状细胞,CD56dim自然杀伤细胞,γδT细胞,未成熟B细胞,浆细胞样树突状细胞,2型辅助T细胞,活化的CD4T细胞和1型T辅助细胞。通过在线数据库分析鉴定了Has_circ_0005073-miRNA-543和AKR1C1-miRNA-543。因此,我们在AAA中建立了has_circ_0005073/miRNA-543/AKR1C1轴。我们发现AKR1C1在正常组和AAA组之间差异表达。基于AKR1C1,我们构建了has_circ_0005073/miRNA-543/AKR1C1轴来分析AAA。
    Abdominal aortic aneurysm (AAA) is a cardiovascular disease that seriously threatens human health and brings huge economic burden. At present, its pathogenesis remains unclear and its treatment is limited to surgical treatment. With the deepening and analysis of studies on the mechanism of ferroptosis, a new idea has been provided for the clinical management of AAA patients, including diagnosis, treatment and prevention. Therefore, this paper aims to construct a competitive endogenous RNA (ceRNA) regulatory axis based on ferroptosis to preliminarily explore the pathogenesis and potential therapeutic targets of AAA. We obtained upregulated and downregulated ferroptosis-related DEGs (FRGs) from GSE144431 dataset and 60 known ferroptosis-related genes. Pearson correlation analysis was used to find aldoketone reductase 1C (AKR1C1) in AAA samples. Enrichment analysis of these genes was performed via Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). Correlation test between immune cells and AKR1C1 was investigated through single-sample gene set enrichment analysis (ssGSEA). The AKR1C1-miRNA pairs were predicted by the TargetScan database and miRWalk database. Circular RNA (CircRNA)-miRNA pairs were selected by the CircInteractome database. Overlapping miRNA between circRNA-miRNA and AKR1C1-miRNA pairs was visualized by Venn diagram. Finally, the circRNA-miRNA-mRNA axis was constructed by searching for upstream circRNA and downstream mRNA of overlapping miRNA. Only one downregulated AKR1C1 gene was found in GSE144431 and 60 ferroptosis-related genes. Functional Enrichment and Pathway Analysis of AKR1C1-related genes were further explored, and it was observed that they were mainly enriched in \"response to oxidative stress,\" \"glutathione biosynthetic process\" and \"nonribosomal peptide biosynthetic process,\" \"Ferroptosis,\" \"Glutathione metabolism\" and \"Chemical carcinogenesis-reactive oxygen species.\" They were also found to be significantly associated with most immune cells, including Activated Dendritic cells, CD56dim Natural killer cells, Gamma Delta T cells, Immature B cells, Plasmacytoid dendritic cell, Type 2 T helper cell, Activated CD4 T cell and Type 1 T helper cell. Has_circ_0005073-miRNA-543 and AKR1C1-miRNA-543 were identified by Online Database analysis. Therefore, we have established the has_circ_0005073/miRNA-543/AKR1C1 axis in AAA. We found AKR1C1 was differentially expressed between normal and AAA groups. Based on AKR1C1, we constructed the has_circ_0005073/miRNA-543/AKR1C1 axis to analyze AAA.
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    文章类型: Journal Article
    脊髓损伤(SCI)是一种严重的中枢神经系统疾病,致残率和死亡率高,病理生理机制复杂。微小RNA(miRNA),作为一种非编码RNA,在SCI中发挥着重要作用。miRNA参与炎症反应的调节,氧化应激,轴突再生,并与长链非编码RNA(lncRNA)和环状RNA(circRNA)相互作用,调控SCI的病理生理过程。本文综述了SCI后miRNA表达的变化,综述了miRNA在SCI中的靶向作用机制及miRNA靶向药物的研究现状,为SCI的基础和临床研究提供新靶点和新视野。
    Spinal cord injury (SCI) is a serious central nervous system disease with high disability and mortality rates and complex pathophysiologic mechanisms. MicroRNA (miRNA), as a kind of non-coding RNA, plays an important role in SCI. miRNA is involved in the regulation of inflammatory response, oxidative stress, axonal regeneration, and apoptosis after SCI, and interacts with long non-coding RNA (lncRNA) and circular RNA (circRNA) to regulate the pathophysiological process of SCI. This paper summarizes the changes in miRNA expression after SCI, and reviews the targeting mechanism of miRNA in SCI and the current research status of miRNA-targeted drugs to provide new targets and new horizons for basic and clinical research on SCI.
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  • 文章类型: Journal Article
    环状RNA(circularRNAs,circRNAs)是最近发现的一类新的内源性RNA,与各种疾病的发展有关。包括他们证实参与几种癌症的进展。不幸的是,circRNAs在乳腺癌中的异常表达和功能有待进一步研究。本文旨在阐明circHSDL2在乳腺癌恶性进展中的作用及其分子机制。从数据库中分析了circRNAs在乳腺癌组织中相对于正常乳腺组织和乳腺癌患者外泌体中相对于健康女性的差异表达谱,以鉴定潜在的功能性circRNAs。选择CircHSDL2进行进一步研究。细胞增殖,进行迁移和侵袭分析以评估circHSDL2过表达对乳腺癌细胞的影响。进行生物信息学测试和双荧光素酶报告基因实验以探索circHSDL2与miRNA之间的相互作用。通过蛋白质组学分析和蛋白质印迹进一步研究下游靶基因。通过裸鼠异种移植实验评估circHSDL2对体内乳腺癌的影响。功能分析显示circHSDL2过表达促进了分裂,运动,和乳腺癌细胞在体内和体外的侵袭。机械上,circHSDL2充当miR-7978的海绵,影响ZNF704的表达,从而调节乳腺癌细胞中的Hippo途径。总之,circHSDL2通过miR-7978/ZNF704轴调节Hippo途径以促进乳腺癌的恶性。这可能是潜在的生物标志物和治疗靶标。
    Circular RNAs (circRNAs) are a new group of endogenous RNAs recently found to be involved in the development of various diseases, including their confirmed involvement in the progression of several types of cancers. Unluckily, the abnormal expression and functions of circRNAs in breast cancer shall be further investigated. This work aims to elucidate the action and molecular mechanism of circHSDL2 in the malignant progression of breast cancer. Differential expression profiles of circRNAs in breast cancer tissues relative to normal breast tissues and in the exosomes of breast cancer patients compared to healthy women were analyzed from databases to identify potentially functional circRNAs. CircHSDL2 was selected for further investigation. Cell proliferation, migration and invasion assays were done to assess the effect of circHSDL2 overexpression on breast cancer cells. Bioinformatics test and dual-luciferase reporter experiments were done to explore the interaction between circHSDL2 and miRNA. Downstream target genes were further investigated through proteomics analysis and Western blotting. The influence of circHSDL2 on breast cancer in vivo was evaluated through xenograft experiments in nude mice. Functional analysis demonstrated circHSDL2 overexpression promoted the division, movement, and invasion of breast cancer cells both in vivo and in vitro. Mechanistically, circHSDL2 acted as a sponge for miR-7978 to affect ZNF704 expression and thereby regulate the Hippo pathway in breast cancer cells. In conclusion, circHSDL2 regulates the Hippo pathway through the miR-7978/ZNF704 axis to facilitate the malignancy of breast cancer. This may be a potential biomarker and treatment target.
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  • 文章类型: Journal Article
    暂无摘要。
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  • 文章类型: Journal Article
    子宫内膜癌是21世纪女性最常见的恶性肿瘤之一。其死亡率每年都在增加。目前,只有在活检后才有可能诊断为EC.然而,有必要寻找一种新的生物标志物,以有助于非侵入性的方式诊断和治疗EC。环状RNA(circularRNAs)很小,共价闭合球形和稳定的长非编码RNA(lncRNAs)分子,它们在体液和人体组织中都很丰富,并以各种方式表达。考虑到EC的新分子分类,许多研究已经出现,描述对EC中circRNAs的功能和机制的新见解。在这篇评论文章中,我们专注于EC的问题及其划分的分子方面,以及生物发生,功能,以及circRNAs在EC中的诊断和临床意义。
    Endometrial cancer (EC) is one of the most common malignant tumors among women in the 21st century, whose mortality rate is increasing every year. Currently, the diagnosis of EC is possible only after a biopsy. However, it is necessary to find a new biomarker that will help in both the diagnosis and treatment of EC in a non-invasive way. Circular RNAs (circRNAs) are small, covalently closed spherical and stable long non-coding RNAs (lncRNAs) molecules, which are abundant in both body fluids and human tissues and are expressed in various ways. Considering the new molecular classification of EC, many studies have appeared, describing new insights into the functions and mechanisms of circRNAs in EC. In this review article, we focused on the problem of EC and the molecular aspects of its division, as well as the biogenesis, functions, and diagnostic and clinical significance of circRNAs in EC.
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  • 文章类型: Journal Article
    T淋巴细胞在抗肿瘤免疫中起关键作用,但是它们的耗尽对恶性细胞的免疫逃避构成了重大挑战。环状RNA(circularRNAs),以它们的共价闭环结构为特征,已经成为肿瘤景观中的关键监管者。最近的研究强调了它们在细胞过程中的多方面作用,包括基因表达调控和蛋白质功能调控,经常在癌症中受到破坏。在这次审查中,我们系统地探讨了circRNAs与肿瘤微环境中T细胞调节之间复杂的相互作用。通过解剖circRNAs影响T细胞衰竭的调控机制,我们旨在揭示免疫逃避和T细胞功能障碍的关键通路.这些见解可以提供针对circRNA介导的分子途径的创新免疫治疗策略。此外,我们讨论了circRNAs作为治疗反应预测的生物标志物和作为干预靶标的翻译潜力。我们的综合分析旨在通过促进精准免疫疗法的发展来增强对肿瘤微环境中免疫逃避动力学的理解。
    T lymphocytes play a critical role in antitumor immunity, but their exhaustion poses a significant challenge for immune evasion by malignant cells. Circular RNAs (circRNAs), characterized by their covalently closed looped structure, have emerged as pivotal regulators within the neoplastic landscape. Recent studies have highlighted their multifaceted roles in cellular processes, including gene expression modulation and protein function regulation, which are often disrupted in cancer. In this review, we systematically explore the intricate interplay between circRNAs and T cell modulation within the tumor microenvironment. By dissecting the regulatory mechanisms through which circRNAs impact T cell exhaustion, we aim to uncover pathways crucial for immune evasion and T cell dysfunction. These insights can inform innovative immunotherapeutic strategies targeting circRNA-mediated molecular pathways. Additionally, we discuss the translational potential of circRNAs as biomarkers for therapeutic response prediction and as intervention targets. Our comprehensive analysis aims to enhance the understanding of immune evasion dynamics in the tumor microenvironment by facilitating the development of precision immunotherapy.
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  • 文章类型: Journal Article
    蛋壳颜色起着重要的生物学作用,吸引了鸡蛋零售商和研究人员的关注。然而,非编码RNA是否参与不同蛋壳颜色之间的色素沉积仍然未知。在这项研究中,RNA测序用于分析长顺鸡蓝壳母鸡的子宫腺转录组(CircRNA和miRNA),产生四种不同的蛋壳色鸡蛋,包括深蓝色PK(DB)和浅蓝色(LB)。深棕色和绿色(介于蓝色和粉红色之间,DP)和粉红色(p)。我们发现miR-192-x,靶向SLC16a7,在DB中表达,DP,和LB组与PK组相比,这表明miR-192-x可能在蓝蛋壳颜色中起作用。KEGG和GO分析表明,在深色和浅蓝色蛋壳鸡中检测到具有靶向基因的“代谢途径”,例如BLVRA和HMOX1,这证实了胆绿素和HO-1的不同比例参与了蓝色的沉积。正如连通性分析所注释的那样,RASGRF1和RASGRF2,属于RASGRF家族,参与Ras信号通路,在细胞生长中起着重要作用,分化,转移和凋亡。我们的发现丰富了circRNA的数据库,鸡子宫组织的miRNAs和基因,这将有助于加速蓝蛋壳色层的分子选择。
    Eggshell color plays important biological roles and attracts the attention of both egg retailers and researchers. However, whether non-coding RNAs are involved in pigment deposition among different eggshell colors remains unknown. In this study, RNA sequencing was used to analyse the uterine gland transcriptome (CircRNA and miRNA) of Changshun chicken blue-shell hens producing four different eggshell color eggs including dark blue PK(DB) and light blue (LB), dark brown and greenish (between blue and pink, DP) and pink (p). We found that miR-192-x, targeting SLC16a7, was expressed in DB, DP, and LB groups compared with the PK group, which indicates that miR-192-x may play a role in the blue eggshell color. KEGG and GO analyses showed that the \"metabolic pathways\" with targeted genes such BLVRA and HMOX1 were detected in dark and light blue color eggshell chickens, which confirms the different ratios of biliverdin and HO-1 involved in the deposition of blue color. As annotated by connectivity analysis, RASGRF1 and RASGRF2, belonging to the RASGRF family, are involved in the Ras signaling pathway, which plays an important role in cell growth, differentiation, metastasis and apoptosis. Our findings enrich the database of circRNA, miRNAs and genes for chicken uterine tissue, which will be useful in accelerating molecular selection for blue eggshell color layers.
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  • 文章类型: Journal Article
    肾间质纤维化(RIF)是慢性肾脏病(CKD)的经典病理生理过程。然而,RIF的潜在机制尚不清楚.本研究发现一种新型环状RNA,cirInpp5b,通过高通量测序可能参与RIF。随后的实验表明,在UUO小鼠肾脏组织和TGF-β1处理的近端肾小管细胞中,circInpp5b减少。circInpp5b的过表达抑制了UUO小鼠中的RIF,并阻止了TGF-β1处理的近端肾小管细胞中的细胞外基质(ECM)沉积。此外,circInpp5b的过表达下调了DDX1的蛋白水平。机械上,circInpp5b与DDX1蛋白结合并促进其溶酶体降解。总的来说,我们的研究结果表明,circInpp5b通过与DDX1蛋白结合并促进其溶酶体降解来改善RIF。
    Renal interstitial fibrosis (RIF) is a classic pathophysiological process of chronic kidney disease (CKD). However, the mechanisms underlying RIF remain unclear. The present study found that a novel circular RNA, cirInpp5b, might be involved in RIF by high-throughput sequencing. Subsequent experiments revealed that circInpp5b was reduced in UUO mouse kidney tissues and TGF-β1-treated proximal tubular cells. The overexpression of circInpp5b inhibited RIF in UUO mice and prevented extracellular matrix (ECM) deposition in TGF-β1-treated proximal tubular cells. Furthermore, overexpression of circInpp5b down-regulated the protein level of DDX1. Mechanistically, circInpp5b bound to the DDX1 protein and promoted its lysosomal degradation. Collectively, the findings of our study demonstrate that circInpp5b ameliorates RIF by binding to the DDX1 protein and promoting its lysosomal degradation.
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  • 文章类型: Journal Article
    背景:现有研究发现,环状RNA(circRNA)充当微RNA(miRNA)的海绵,以控制下游基因。然而,circRNAs在人肾透明细胞癌(ccRCC)中的具体功能和作用机制尚未得到彻底研究.
    方法:来自在线数据库的患者队列用于筛选候选circRNAs,而另一个来自我们医院的队列进行验证。CircSOD2被确定为潜在的致癌靶标,并通过各种试验研究了ccRCC进展过程中的相关特征。使用生物信息学鉴定了含有下游miRNA及其靶基因的正反馈环,并通过荧光素酶报告基因测定进行了验证。RNA下拉,和高通量测序。
    结果:CircSOD2表达在肿瘤样本中升高,并且与ccRCC患者的总生存期(OS)和肿瘤分期显着相关,出现在增强的扩散中,入侵,和肿瘤细胞的迁移。miR-532-3p通过与circSOD2竞争结合,可以促进PAX5的表达和ccRCC的进展,这种调节可以通过miR-532-3p抑制剂来挽救。
    结论:一种新颖的正反馈回路,PAX5/circSOD2/miR-532-3p/PAX5在研究中被鉴定,提示环可能在ccRCC患者的诊断和预后预测中起重要作用。
    BACKGROUND: Existing studies have found that circular RNAs (circRNAs) act as sponges for micro RNAs (miRNAs) to control downstream genes. However, the specific functionalities and mechanisms of circRNAs in human clear cell renal cell carcinoma (ccRCC) have yet to be thoroughly investigated.
    METHODS: Patient cohorts from online databases were used to screen candidate circRNAs, while another cohort from our hospital was obtained for validation. CircSOD2 was identified as a potential oncogenic target, and its relevant characteristics were investigated during ccRCC progression through various assays. A positive feedback loop containing downstream miRNA and its target gene were identified using bioinformatics and validated by luciferase reporter assays, RNA pull-down, and high-throughput sequencing.
    RESULTS: CircSOD2 expression was elevated in tumor samples and significantly correlated with overall survival (OS) and the tumor stage of ccRCC patients, which appeared in the enhanced proliferation, invasion, and migration of tumor cells. Through competitive binding to circSOD2, miR-532-3p can promote the expression of PAX5 and the progression of ccRCC, and such regulation can be salvaged by miR-532-3p inhibitor.
    CONCLUSIONS: A novel positive feedback loop, PAX5/circSOD2/miR-532-3p/PAX5 was identified in the study, indicating that the loop may play an important role in the diagnosis and prognostic prediction in ccRCC patients.
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  • 文章类型: Journal Article
    背景:目前,已经发现许多患者对放射治疗产生了抗性,大大降低了放疗的效果,进而影响预后。CircRNAs参与多种肿瘤细胞放射敏感性的调节。因此,本研究的主要目的是探讨CircRNA_101491对ESCC放射敏感性的调节作用及其相关机制。
    方法:我们通过梯度剂量法建立了ESCC耐辐射细胞系(KYSE150R细胞),并在体外测试了KYSE150R细胞与亲本细胞之间KYSE150的差异。然后,在敲除CircRNA_101491的表达后,进行了一系列体外实验,以验证CircRNA_101491对KYSE150R细胞表型和放射敏感性的影响,并进一步分析了相关的监管机制。此外,我们还使用裸鼠移植瘤模型来研究CircRNA_101491对ESCC体内放射敏感性的影响。
    结果:根据一系列体外实验,我们证实KYSE150R细胞失去上皮表型,获得间质细胞样表型,发现CircRNA_101491在KYSE150R细胞中高表达。此外,我们发现,敲低CircRNA_101491的表达将解除miR-125a-5p的抑制,然后逆转EMT的过程,加速细胞凋亡的过程,从而在放射增敏中发挥作用。裸鼠移植瘤的体内实验还表明,敲低CircRNA_101491的表达可以增强ESCC的放射敏感性。
    结论:结论:我们证实干扰CircRNA_101491的表达可以减轻miR-125a-5p的抑制,从而逆转间质表型的过程,加速细胞凋亡的过程,增强ESCC的放射敏感性。
    BACKGROUND: At present, it has been found that many patients have acquired resistance to radiotherapy, which greatly reduces the effect of radiotherapy and further affects the prognosis. CircRNAs is involved in the regulation of radiosensitivity of many kinds of tumor cells. Therefore, the main purpose of this study is to explore the regulatory effect of CircRNA_101491 on radiosensitivity of ESCC and its related mechanism.
    METHODS: We established ESCC radiation-resistant cell line (KYSE150R cell) by gradient dose method, and tested the difference of KYSE150 between KYSE150R cell and parent cell in vitro. Then, after knocking down the expression of CircRNA_101491, a series of in vitro experiments were conducted to verify the effects of CircRNA_101491 on the phenotype and radiosensitivity of KYSE150R cells, and further analyzed the related regulatory mechanism. In addition, we also used the model of transplanted tumor in nude mice to investigate the effect of CircRNA_101491 on the radiosensitivity of ESCC in vivo.
    RESULTS: According to a series of in vitro experiments, we confirmed that KYSE150R cells lost the epithelial phenotype and obtained interstitial cell-like phenotype, and found that CircRNA_101491 was highly expressed in KYSE150R cells. In addition, we found that knocking down the expression of CircRNA_101491 will lift the inhibition of miR-125a-5p, and then reverse the process of EMT, accelerate the process of apoptosis, thus play a role in radiosensitization. The in vivo experiment of transplanted tumor in nude mice also showed that knocking down the expression of CircRNA_101491 could enhance the radiosensitivity of ESCC.
    CONCLUSIONS: In conclusion, we confirmed that interfering with the expression of CircRNA_101491 can relieve the inhibition of miR-125a-5p, thus reverse the process of interstitial phenotype, accelerate the process of apoptosis, and enhance the radiosensitivity of ESCC.
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