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CircR2Disease v2.0:An Updated Web Server for Experimentally Validated circrna–disease Associations and Its Application

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Genomics, Proteomics & Bioinformatics 2022年第3期20卷 435-445页

作者： Chunyan Fan Xiujuan Lei Jiaojiao Tie Yuchen Zhang Fang-Xiang Wu Yi Pan School of Computer Science Shaanxi Normal UniversityXi’an 710119China Division of Biomedical Engineering University of SaskatchewanSaskatoonSK S7N 5A9Canada Department of Computer Science Georgia State UniversityAtlantaGA 30302USA

With accumulating dysregulated circular RNAs(circrnas)in pathological processes,the regulatory functions of circrnas,especially circrnas as microRNA(miRNA)sponges and their interactions with RNA-binding proteins(RBPs),have been widely ***,the collected information on experimentally validated circrna-disease associations is only ***,an updated CircR2Disease database providing a comprehensive resource and web tool to clarify the relationships between circrnas and diseases in diverse species is ***,we present an updated CircR2Disease v2.0 with the increased number of circrna-disease associations and novel ***2Disease v2.0 provides more than 5-fold experimentally validated circrna-disease associations compared to its previous *** version includes 4201 entries between 3077 circrnas and 312 disease ***,the information of circrna-miRNA,circrna-miRNA-target,and circrna-RBP interactions has been manually collected for various ***,the gene symbols of circrnas and disease name IDs can be linked with various nomenclature *** descriptions such as samples and journals have also been integrated into the updated ***,CircR2Disease v2.0 can serve as a platform for users to systematically investigate the roles of dysregulated circrnas in various diseases and further explore the posttranscriptional regulatory function in ***,we propose a computational method named circDis based on the graph convolutional network(GCN)and gradient boosting decision tree(GBDT)to illustrate the applications of the CircR2Disease v2.0 ***2Disease v2.0 is available at http://***/CircR2Disease_v2.0 and https://***/bioinforlab/CircR2Disease-v2.0.

关键词： circrna circrna-disease association Graph convolutional network Gradient boosting decision tree Machine learning

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Differential circrna Expression Profiles in PK-15 Cells Infected with Pseudorabies Virus Type Ⅱ

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Virologica Sinica 2021年第1期36卷 75-84页

作者： Haimin Li Wen Tang Yulan Jin Weiren Dong Yan Yan Jiyong Zhou MOA Key Laboratory of Animal Virology Center of Veterinary SciencesZhejiang UniversityHangzhou 310058China

Circular RNAs(circ RNAs)belong to a class of non-coding RNAs with diverse biological ***,little is known about their roles in case of pseudorabies virus(Pr V)***,we analyzed the expression profile of host circ RNAs from a virulent Pr V type II strain DX(Pr V-DX)infected and an attenuated g E/TK deficient(g E-TK-Pr V)strain of Pr V infected PK-15 *** RNAs were identified by findcirc and analyzed with DESeq *** with the mock cells,449 differentially expressed(DE)circ RNAs(233 down-regulated and 216 up-regulated)from Pr V-DX infected and578 DE circ RNAs(331 down-regulated and 247 up-regulated)from g E-TK-Pr V infected PK-15 cells were *** addition,459 DE circ RNAs(164 down-regulated and 295 up-regulated)between the Pr V-DX and g E-TK-Pr V infected cells were *** expression patterns of 13 circ RNAs were validated by reverse transcription quantitative real-time PCR(RT-q PCR)and results were similar as of *** putative target mi RNA binding sites of DE circ RNAs were predicted by using mi Randa and ps *** circ RNA-mi RNA-m RNA network was constructed and certain mi RNAs that have possible roles in antiviral immune response,such as mi R-210 and mi R-340,were *** and KEGG pathway analysis demonstrated that DE circ RNAs were enriched in the processes such as cellular metabolism,protein binding,RNA degradation and regulation of actin ***,these findings might provide the useful information for a better understanding of mechanisms underlying the interaction between Pr V-II and host cells.

关键词： Pseudorabies virus infection RNA-seq circrna

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Multifaceted roles of complementary sequences on circrna formation

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Frontiers of Electrical and Electronic Engineering in China 2017年第3期5卷 205-209页

作者： Qin Yang Ying Wang Li Yang CAS Key Laboratory of Computational Biology Collaborative Innovation Center of Genetics and Development CAS-MPG Partner Institute for Computational Biology Shanghai Institutes for Biological Sciences Chinese Academy of Sciences University of Chinese Academy of Sciences Shanghai 200031 China School of Life Science and Technology ShanghaiTech University Shanghai 201210 China

Background： Circular RNAs （circrnas） from back-spliced exon（s） are characterized by the covalently closed loop feature with neither 5＇ to 3＇ polarity nor polyadenylated tail. By using specific computational approaches that identify reads mapped to back-splice junctions with a reversed genomic orientation, ten thousands of cireRNAs have been recently re-identified in various cell lines/tissues and across different species. Increasing lines of evidence suggest that back-splicing is catalyzed by the canonical spliceosomal machinery and modulated by cis-elements and trans-factors. Results： In this mini-review, we discuss our current understanding of circrna biogenesis regulation, mainly focusing on the complex regulation of complementary sequences, especially Alus in human, on circrna formation. Conclusions： Back-splicing can be significantly facilitated by RNA pair formed by orientation-opposite complementary sequences that juxtapose flanking introns of circularized exon（s）. RNA pair formed within individual introns competes with RNA pair formed across flanking introns in the same gene locus, leading to distinct choices for either canonical splicing or back-splicing. Multiple RNA pairs that bracket different circle-forming exons compete for alternative back-splicing selection, resulting in multiple circrnas generated in a single gene locus.

关键词： circrna circrna biogenesis back-splicing cis-elements complementary sequences Alu

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Detection of Prognostic Biomarkers for Hepatocellular Carcinoma through circrna-associated CeRNA Analysis

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Journal of Clinical and Translational Hepatology 2022年第1期10卷 80-89页

作者： Li Han Maolong Wang Yuling Yang Hanlin Xu Lili Wei Xia Huang Department of Nursing Affiliated Hospital of Qingdao UniversityQingdaoShandongChina Department of Thoracic Surgery The Affiliated Hospital of Qingdao UniversityQingdaoShandongChina Department of Infectious diseases The Affiliated Hospital of Qingdao UniversityQingdaoShandongChina

Background and Aims:The prognosis of hepatocellular carcinoma(HCC)is extremely poor;therefore,there is an urgent need for novel prognostic molecular biomarkers of *** current investigation utilized circular(circ)RNA-associated competing endogenous(ce)RNAs analysis in order to identify significant prognostic biomarkers of ***:circrnas and mRNAs that were differentially expressed between normal and HCC tissues were *** respective functions were predicted with Gene Ontology enrichment and Kyoto Encyclopedia of Genes and Genomes enrichment analyses.A nomogram was used for model ***:A ceRNA network composed of differentially expressed circrnas and mRNAs was *** hub nodes in the ceRNA network were hsa_circ_0004662,hsa_circ_0005735,hsa_circ_0006990,hsa_circ_0018403 and hsa_circ_*** using this in-formation,a prognostic risk assessment tool was developed based on the expressions of seven genes(PLOD2,TARS,RNF19B,CCT2,RAN,C5orf30 and MCM10).Furthermore,multivariate Cox regression analysis revealed risk and T-stage parameters as independent prognostic *** nomograms that were constructed from risk and T-stage groups were used to further assess the prediction of HCC patient survival *** nomogram,which consisted of risk and T-stage scores assessment models,was found to be an independent factor for predicting prognosis of ***:Five circrnas,including hsa_circ_0004662,hsa_circ_0005735,hsa_circ_0006990,hsa_circ_0018403 and hsa_circ_0100609,that may play key roles in the pro-gression of HCC were *** gene signatures were identified,which were associated with the aforemen-tioned circrnas,including PLOD2,TARS,RNF19B,CCT2,RAN,C5orf30 and MCM10,all of which were significant genes involved in the pathophysiology of *** genes may be used as a prognosticating tool in HCC patients.

关键词： Hepatocellular carcinoma circrna Signature Prognosis CeRNA

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Identification of circrna/miRNA/mRNA regulatory net-work involving(+)-catechin ameliorates diabetic nephropathy mice

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Food Science and Human Wellness 2022年第3期11卷 660-668页

作者： Chao Chen Dina Zhu Shuai Zhang Wensheng Zhang Zhuhai Branch of State Key Laboratory of Earth Surface Processes and Resource Ecology Advanced Institute of Natural SciencesBeijing Normal UniversityZhuhai 519087China Engineering Research Center of Natural Medicine Ministry of EducationAdvanced Insti-tute of Natural SciencesBeijing Normal UniversityZhuhai 519087China International Cooperation Laboratory of Molecular Medicine Academy of Chinese Medical SciencesZhejiang Chinese Medical UniversityHangzhou 310053China Beijing Key Laboratory of Traditional Chinese Medicine Protection and Utilization Faculty of Geographical ScienceBeijing Normal UniversityBeijing 100875China

(+)-Catechin(CE)is mainly found in green and black tea and has many biological effects,such as antiinflammatory,anti-cancer,anti-viral effects,protecting human organs,especially the *** study aims to identify the circrnas induced by CE in db/db mice and their roles in diabetic nephropathy *** the db/db mice were treated with CE,RNA-seq was performed to identify the differentially expressed circrna and *** ceRNA regulatory network was constructed and analyzed using bioinformatics software and public databases(Cytoscape,Clue GO,Mi RWalk,STRING,et al.).Our results revealed that 6 differentially expressed circrnas are most associated with the cholinergic synapse,neurotrophin signaling pathway,and insulin signaling *** these,circrna.5549 and circrna.4712 might regulate Cd36,Cyp26 b1,C8 a,Cyp2 j13,Grem2 genes through ceRNA regulatory mechanism in the presence of CE *** expanded network of proteins interacting with these 5 genes shows that the TGF-βsignaling pathway,signaling pathways regulating pluripotency of stem cell,fat digestion and absorption,and PPAR signaling pathway was highly ***,circrna.5549 and circrna.4712 exhibit a promotive function in CE-treated db/db mice,especially in circrna.5549/miR-29a-5P/Cd36 regulatory network,and this evidence suggest that their ceRNA regulatory network might be a therapeutic target for DN in humans.

关键词： Catechin Diabetic nephropathy circrna miRNA ceRNA

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Identification of the circrna-miRNA-mRNA regulatory network and its prognostic effect in colorectal cancer

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World Journal of Clinical Cases 2021年第18期9卷 4520-4541页

作者： Teng-Fei Yin Dong-Yan Zhao Yuan-Chen Zhou Qian-Qian Wang Shu-Kun Yao Graduate school Peking University China-Japan Friendship School of Clinical MedicineBeijing 100029China Graduate School Peking Union Medical College and Chinese Academy of Medical SciencesBeijing 100730China Department of Gastroenterology China-Japan Friendship HospitalBeijing 100029China

BACKGROUND The high morbidity and mortality of colorectal cancer(CRC)have posed great threats to human *** RNA(circrna)and microRNA(miRNA),acting as competing endogenous RNAs(ceRNAs),have been found to play vital roles in ***,the biological function of ceRNAs in CRC pathogenesis and prognosis remains largely *** To identify the CRC-specific circrna-miRNA-mRNA regulatory network and uncover the subnetwork associated with its *** circrnas,miRNAs and mRNAs differentially expressed(DE)in CRC tissues were selected by expression file analysis in the Gene Expression Omnibus(GEO)database,and the downstream target molecules of circrnas and miRNAs were ***,the intersection of differentially expressed RNA molecules with the predicted targets was determined to obtain a ceRNA *** ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analyses were conducted to elucidate the possible mechanism of pathogenesis.A survival analysis using the gene profiles and clinical information in The Cancer Genome Atlas(TCGA)database was performed to identify the mRNAs associated with the clinical outcome of CRC patients and construct a prognostic *** We downloaded three datasets(GSE126095,GSE41655 and GSE41657)of largescale CRC samples from the GEO *** were 55 DEcircrnas,114 DEmiRNAs and 267 DEmRNAs in CRC tissues compared with normal *** intersecting these molecules with predicted targets,19 circrnas,13 miRNAs and 28 mRNAs were chosen to develop a circrna-miRNA-mRNA *** and KEGG functional enrichment analyses indicated that the retinol metabolic process,leukocyte chemotaxis,extracellular matrix remodeling,endoplasmic reticulum stress,alcohol dehydrogenase activity,gastric acid secretion,nitrogen metabolism and NOD-like receptor signaling pathway might participate in the tumorigenesis of *** verifying the identified mRNA effect in the TCGA database,we finally

关键词： circrna miRNA Network Colorectal cancer Prognosis Biomarkers

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失重性骨丢失的关键调控circrna筛选与ceRNA网络构建

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空军军医大学学报 2025年第1期46卷 17-23页

作者：王栋李程飞李曦赵子怡李嘉翔闫铭王永春空军军医大学航空航天医学系航空航天医学训练教研室陕西西安710032 空军军医大学西京医院骨科陕西西安710032

目的通过高通量测序(HTS)技术筛选模拟失重环境下骨髓间充质干细胞(BMSCs)中环状RNA(circrna)的差异表达谱,对差异表达circrna(DEcircrna)进行生物信息学分析并进行部分验证,从分子水平探讨失重性骨丢失的可能机制。方法利用骨形态发生... 详细信息

目的通过高通量测序(HTS)技术筛选模拟失重环境下骨髓间充质干细胞(BMSCs)中环状RNA(circrna)的差异表达谱,对差异表达circrna(DEcircrna)进行生物信息学分析并进行部分验证,从分子水平探讨失重性骨丢失的可能机制。方法利用骨形态发生蛋白2诱导小鼠BMSCs成骨分化,分为地面对照组(Ground组)和模拟微重力组(SMG组)。通过Illumina NovaSeq 6000对样本总RNA进行转录组测序并筛选与分析两组差异表达基因(DEGs),进一步构建circrna-miRNA-mRNA相互作用的竞争性内源RNA(ceRNA)调控网络。结果通过比较两组共鉴定出18个DEcircrna,其中7个上调和11个下调circrna。GO和KEGG富集分析结果显示,这些DEcircrna的源基因主要富集在调节细胞分化和调节细胞增殖等功能,并显著富集于MAPK信号通路和细胞衰老等信号通路。CeRNA调控网络的建立可更深入了解DEcircrna的生物学作用。通过qRT-PCR方法验证了6个DEcircrna,其结果与测序结果一致。结论本研究通过HTS和生物信息学方法筛选并阐明了18个DEcircrna在失重性骨丢失中的潜在生物学作用,为后续研究失重性骨丢失的发生机制和临床治疗提供了新的思路。

关键词：模拟失重失重性骨丢失骨髓间充质干细胞高通量测序 circrna

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circrna调控放疗抵抗相关通路的作用机制研究进展

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中华放射医学与防护杂志 2021年第4期41卷 304-308页

作者：向婧黄瑞雪中南大学湘雅公共卫生学院劳动卫生与环境卫生学系长沙410078

放射治疗是目前临床上治疗恶性肿瘤的重要手段,但是肿瘤细胞由此产生的放疗抵抗不仅严重限制了肿瘤放射治疗的效果,导致患者预后不良,最终可能造成患者出现肿瘤转移复发等状况.环状RNA (circrna)是非编码RNA中的新成员,具有高度特异性... 详细信息

放射治疗是目前临床上治疗恶性肿瘤的重要手段,但是肿瘤细胞由此产生的放疗抵抗不仅严重限制了肿瘤放射治疗的效果,导致患者预后不良,最终可能造成患者出现肿瘤转移复发等状况.环状RNA (circrna)是非编码RNA中的新成员,具有高度特异性、稳定性和保守性.本文从circrna对放疗抵抗相关信号通路影响入手,从DNA损伤修复通路、EMT(上皮间质转化)过程、Wnt通路、肿瘤干细胞等通路变化的角度,梳理circrna在肿瘤细胞对放疗抵抗的作用机制,为进一步研究circrna提供有价值的线索.

关键词： circrna 放疗抵抗癌症

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circrna在肺癌诊断与发生发展及耐药中的作用进展

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中国肺癌杂志 2019年第8期22卷 532-536页

作者：陈天翔杨运海上海交通大学附属胸科医院肿瘤科(胸外专业)上海市肺部肿瘤临床医学中心

肺癌在全球范围内的致死率一直居高不下。近年来针对多种分子分型的靶向药物已成为中晚期肺癌治疗的新有效手段,但是肺癌在早期诊断以及长期有效的治疗上仍然面临着严峻的挑战。环状RNA(circular RNA,circrna)是一类具有环形结构的独特... 详细信息

肺癌在全球范围内的致死率一直居高不下。近年来针对多种分子分型的靶向药物已成为中晚期肺癌治疗的新有效手段,但是肺癌在早期诊断以及长期有效的治疗上仍然面临着严峻的挑战。环状RNA(circular RNA,circrna)是一类具有环形结构的独特RNA分子,具有优异的稳定性以及表达特异性。越来越多的研究发现circrna在肿瘤中表达异常,这种异常表达不仅与肿瘤的恶性相关,同时可以参与调控肿瘤进展,为肿瘤的诊断与治疗提供了新的思路。因此,本文就circrna在肺癌中的表达、诊断、预后价值以及发生发展机制展开综述,以期为肺癌的早期诊断与治疗寻找新的靶点。

关键词： circrna MiRNA海绵肺肿瘤

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中国药理学通报 2024年第8期40卷 1462-1473页

作者：崔逸爽郑璇吴亚男么艺涵王珺刘子情孙国贵华北理工大学公共卫生学院河北唐山063210 华北理工大学药学院河北唐山063210 华北理工大学附属医院河北唐山063000

目的通过生物信息学分析震颤响应蛋白(quaking,QKI)参与胃癌(gastric cancer,GC)发生和发展的可能分子机制。研究QKI在GC细胞中的增殖、侵袭和迁移能力。方法联合TCGA和GTEx数据库分析QKI在常见人类癌症样本中的差异表达。分析QKI蛋白... 详细信息

目的通过生物信息学分析震颤响应蛋白(quaking,QKI)参与胃癌(gastric cancer,GC)发生和发展的可能分子机制。研究QKI在GC细胞中的增殖、侵袭和迁移能力。方法联合TCGA和GTEx数据库分析QKI在常见人类癌症样本中的差异表达。分析QKI蛋白表达与肿瘤突变负荷(tumor mutation burden,TMB)评分、微卫星不稳定性(microsatellite instability,MSI)评分以及ESTIMATE评分的相关性,并分析QKI蛋白表达与总生存期(overall survival,OS)、无病生存期(disease free survival,DFS)及无进展生存期(progression free survival,PFS)的相关性。通过生物信息学分析获得可编码DEcircrnas的EMT相关基因,构建QKI-EMT-circrnas调控网络。在TMK1细胞中对差异表达的circrnas和EMT相关基因进行表达验证,并验证敲降QKI后对TMK1细胞的增殖、侵袭和迁移能力的影响。结果QKI在绝大多数肿瘤中差异表达,且与TMB、MSI以及肿瘤微环境(tumour microenvironment,TME)密切相关;QKI可作为高风险因子预测常见人类癌症患者的OS、DFS和PFS。QKI通过调控6个EMT相关基因转录本剪切形成8个circrnas,它们均与胃癌患者预后明显相关。细胞实验表明,相对于正常胃上皮细胞,只有hsa_ccirc_0004015、CALD1和CDK14在TMK1细胞中表达下调。敲降QKI可抑制TMK1细胞的增殖、侵袭和迁移能力。结论QKI通过调控6个EMT相关基因转录本剪切形成circrnas,从而促进GC发生和发展。QKI在TMK1细胞中高表达,敲降QKI可抑制TMK1细胞的增殖、侵袭和迁移能力。

关键词：胃癌 QKI RNA结合蛋白上皮间充质转化 circrna 生物信息学分析

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