简介:AbstractGastric cancer (GC) is a common malignancy and is the third leading cause of cancer-related death. At present, there is no simple and effective screening method for early-stage GC, and the treatment results and prognosis are poor. With the continuous improvement of molecular biology techniques, research on circular RNA (circRNA) has gradually expanded over time. Much data supports the role of circRNA in tumorigenesis. Moreover, due to its structural specificity and biological stability, circRNA is anticipated to be a potential biomarker for tumor diagnosis. Studies have confirmed that circRNA can participate in the proliferation, invasion, metastasis, and apoptosis of GC. These findings will lead to novel directions for the diagnosis and treatment of GC. This article reviews the structure and function of circRNA, summarizes the current studies on circRNA, and discusses the potential diagnostic value of circRNA in GC.
简介:Objective:ThepresentstudyaimedtoinvestigatecircularRNA(circRNA)expressioninuvealmelanoma(UM).Methods:First,weusedmicroarraytocomparetheexpressionprofilesofcircRNAinfiveUMsamplesandfivenormaluveatissues.Next,bioinformaticsanalyses,includinggeneontology(GO)analysisandpathwayanalysis,wereappliedtostudythesedifferentiallyexpressedcircRNAstopredictpathogenicpathwaysthatmaybeinvolved.Quantitativereal-timepolymerasechainreaction(qRT-PCR)in20UMsamplesand20normaluveasampleswasusedtoconfirmthecircRNAexpressionprofilesobtainedfromthemicroarraydata.Finally,weanalyzedtheinteractionbetweenvalidatedcircRNAsandtheirpotentialcancer-associatedmiRNAtargets.Results:Intotal,50,579circRNAs[foldchange(FC)≥2.0;P<0.05],including20,654up-regulatedand29,925down-regulatedcircRNAs,wereidentifiedasdifferentiallyexpressedbetweenUMtissuesandnormaluveatissues.WeusedqRT-PCRtoverifysevendysregulatedcircRNAsindicatedbythemicroarraydata,includinghsacirc0119873,hsacirc0128533,hsacirc0047924,hsacirc0103232,hsa-circRNA10628-6,hsacirc0032148andhsacirc0133460,whichmaybepromisingcandidatestostudyfuturemolecularmechanisms.Conclusions:Thisstudyexplored,forthefirsttime,theabnormalexpressionofcircRNAsinUManddescribedtheexpressionprofileofcircRNAs,providinganewpotentialtargetforthemechanismofUMandfuturetreatmentofUM.
简介:AbstractBackground:Previous studies have demonstrated that various circular RNAs are involved in the malignant proliferation of cancers, such as liver cancer, lung cancer, breast cancer, and others. The potential role of circular RNAs in glioblastoma, however, is still uncertain. In this study, we aimed to study the potential role of hsa_circ _01844 in glioblastoma.Methods:Using reverse transcription-polymerase chain reaction (RT-PCR) method, hsa_circ_01844 expression was measured in five glioblastoma samples and five normal brain samples. To evaluate the potential function of hsa_circ_01844 in glioblastoma, hsa_circ_01844 was overexpressed in glioblastoma cell lines (U251 and U87 cells). Using these two cell lines, in vitro experiments including the flow cytometry assay, 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide assay, Transwell assay, and cell apoptosis assay were performed to investigate the role of hsa_circ_01844 in glioblastoma. Student t test and one-way analysis of variance were used for statistical analysis.Results:The expression of circular RNA hsa_circ_01844 was lower in glioblastoma tissues when compared with the normal brain tissues by RT-PCR method (0.034 ± 0.036 vs. 1.630 ± 0.891, P < 0.001). Using two glioblastoma cell lines, we found that overexpression of hsa_circ_01844 in glioblastoma cells suppressed their proliferation, colony formation, migration, and increased the apoptotic rate compared with empty vector group and blank control group (all P < 0.05).Conclusion:Hsa_circ_01844 shows decreased expression in glioblastoma and its overexpression induces apoptosis and inhibits proliferation, migration, and invasion of glioblastoma cells.
简介:AsanewlydiscoveredtypeofRNA,circularRNAs(circRNAs)arewidespreadthroughouttheeukaryoticgenome.TheexpressionofcircRNAsisregulatedbybothcis-elementsandtrans-factors,andtheexpressionpatternofcircRNAsiscelltype-anddiseasespecific.Similartoothertypesofnon-codingRNAs,functionsofcircRNAsarealsoversatile.CircRNAshavebeenreportedpreviouslytofunctionasmicroRNA(miRNA)sponges,proteinsponges,codingRNAsorscaffoldsforproteincomplexes.Recently,severalcircRNAshavebeenreportedtoplayimportantrolesinhumanmalignancies,includingglioma.Here,wereviewedseveralreportsrelatedtocircRNAsandglioma,aswellasthepotentialdiagnosticandtherapeuticapplicationsofcircRNAsinbraincancer.Ingeneral,somecircRNAs,suchascircSMARCA5andcircCFH,arefoundtobeexpressedinagliomaspecificpattern,thesecircRNAsmaybeusedastumorbiomarkers.Inaddition,somecircRNAshavebeenfoundtoplayoncogenicrolesinglioma(e.g.,circNFIXandcircNT5E),whereasothershavebeenreportedtofunctionastumorsuppressors(e.g.,circFBXW7andcircSHPRH).Furthermore,circRNAisagoodtoolforproteinexpressionbecauseofitshigherstabilitycomparedtolinearRNAs.Thus,circRNAsmayalsobeanidealchoiceforgene/proteindeliveryinfuturebraincancertherapies.TherearesomechallengesincircRNAresearchingliomaandotherdiseases.ResearchrelatedtocircRNAsingliomaiscomparativelynewandmanymysteriesremaintobesolved.
简介:AbstractCircular RNAs (circRNAs) constitute a novel class of endogenous noncoding RNAs characterized by a covalently closed structure and involved in multiple biological processes. The main biological functions and properties of circRNAs can be defined by five features: a "sponging" effect on other RNA species, post-transcriptional regulation, rolling circle translation, generation of pseudogenes, and splicing interference. Although circRNAs were first detected decades ago, the role of circRNAs and the mechanisms underlying their actions remain incompletely characterized. Recently, circRNAs were reported to play indispensable roles in regulating metabolic and signal transduction events controlling the proliferation, migration, and survival of cells. Importantly, many studies demonstrated that dysregulated circRNA expression is associated with the development of multiple diseases, including cancer. In this review, we summarize current knowledge on the roles and mechanisms of circRNAs in cancer and discuss their functions as oncogenes or tumor suppressors in different tumor types.
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简介:BackgroundCircularRNAs(circRNAs)areendogenousnon-codingRNAsthatparticipateinregulatinggeneexpressionindiversebiologicalandpathologicalprocesses.TherolesofcircRNAsinatrialfibrillation(AF)havenotbeenwellelucidated.Inthepresentstudy,circRNAsprofileintheatrialappendagesofpatientswithAFwasexamined.MethodsHematoxylin-eosin(HE)andMassontrichromestainingwasperformedontheatrialappendagesofpatientswithsinusrhythm(SR)orAF.Expressionsoffibrosis,rennin-angiotensin-aldosteronesystem(RAAS)andinflammation-associatedgenesweredeterminedbyquantitativereversetranscriptionPCR(qRT-PCR).CircRNAsexpressionprofileinatrialappendageswasdetectedbycircRNAsmicroarray.qRT-PCRwasalsousedtodeterminetheexpressionof6representativedys-regulatedcircRNAs.PCRproductsofconcernedcircRNAswerefurtheridentifiedbygelelectrophoresisandDNAsequencingassay.ResultsMassontrichromestainingresultshowedthatfibrosiswasincreasedintheatrialappendagesofAFpatients.Thelevelsofcol1a1,Col3a1,fibrinectin-1(FN1),IL1-βandCRPmRNAexpressionweresignificantlyup-regulatedintheatrialappendagesofAFpatients.AcircRNAsarrayrevealedthatcircRNAsweredysregulatedintheatrialappendagesofAFpatients.qRT-PCRresultsdemonstratedthatcircRNA_100395wasup-regulated,circRNA_101270,circRNA_103820,circRNA_104168andcircRNA_100782weredown-regulatedsignificantlyintheatrialappendagesofAFpatientscomparedtoSRpatients.ConclusionsFibrosisandinflammationoccurintheatrialappendagesofAFpatients,whichcouldrelatetocircRNAsdysregulation.
简介:AbstractBackground:Circular RNA (circRNA) is a type of closed circular noncoding RNA (ncRNA), mostly formed by back-splicing or alternative splicing of pre-messenger RNA (mRNA). The aim of this study was to explore the expression profile of circRNA in peripheral blood mononuclear cells (PBMCs) of patients with ankylosing spondylitis (AS) and discover potential molecular markers of AS.Methods:The circRNA microarray technology was used to detect the expression of circRNAs in the peripheral blood of 6 patients with AS and 6 healthy controls (HC). To screen the differentially expressed circRNAs by fold change (FC) and P value, these differentially expressed circRNAs were analyzed by bioinformatics. In 60 cases of AS and 30 cases of HC, 4 circRNAs were subjected to real-time fluorescence quantitative polymerase chain reaction (RT-qPCR), and their correlation with various clinical indicators was analyzed. Finally, the receiver operating characteristic (ROC) curve was used to analyze their potential as AS diagnostic markers.Results:The microarray results showed that there were 1369 significantly differently expressed (P < 0.05, FC > 1.5) circRNAs between the AS and HC groups (675 upregulated and 694 downregulated). The results of bioinformatics analysis suggested that they were mainly involved in "enzyme binding," "adenosine ribonucleotide binding," "MAPK signaling pathway" , etc. The RT-qPCR results showed that the expressions of hsa_circRNA_001544 (U = 486.5, P < 0.05) and hsa_circRNA_102532 (U = 645, P < 0.05) were significantly different between the AS group and the HC group. The AS group was further divided into two subgroups: active AS (ASA) and stable AS (ASS). After analysis, it was found that compared with the HC group, hsa_circRNA_001544 was significantly increased in both ASA (U = 214, P < 0.05) and ASS groups (U = 273, P < 0.05), while hsa_circRNA_008961 (U = 250, P < 0.05) and hsa_circRNA_102532 (U = 295, P < 0.05) were only significantly increased in the ASA group. Furthermore, hsa_circRNA_012732 was significantly different between the ASA and ASS groups (U = 194, P < 0.05), and there was no statistical significance among the remaining groups. Correlation analysis results showed that hsa_circRNA_012732 was negatively correlated with Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), high-sensitivity C-reactive protein (hsCRP), and globulin (GLOB) and positively correlated with lymphocyte count (LY), mean corpusular volume, and albumin (ALB), and hsa_circRNA_008961 was negatively correlated with platelet (PLT) count. ROC curve analysis showed that hsa_circRNA_001544 (95% CI = 0.610-0.831, P < 0.05) and hsa_circRNA_102532 (95% CI = 0.521-0.762, P < 0.05) were statistically significant, and their area under curve (AUC) values were 0.720 and 0.642, respectively.Conclusions:There are differentially expressed circRNAs in PBMCs of AS patients, and they may be involved in the occurrence and development of AS. Among these differentially expressed circRNAs, hsa_circRNA_012732 has the potential to become an indicator of disease activity, and hsa_circRNA_001544 has the potential to become a molecular marker for AS diagnosis.
简介:AbstractBackground:Recent studies have reported circular RNA (circRNA) expression profiles in various tissue types; however, circRNA expression profile in human epicardial adipose tissue (EAT) remains undefined. This work aimed to compare circRNA expression patterns in EAT between the heart failure (HF) and non-HF groups.Methods:RNA-sequencing was carried out to compare circRNA expression patterns in EAT specimens from coronary artery disease cases between the HF and non-HF groups. Quantitative real-time polymerase chain reaction was performed for validation. Comparisons of patient characteristics between the two groups were using t test, Mann-Whitney U test, and Chi-squared test.Results:A total of 141 circRNAs substantially different between the HF and non-HF groups (P < 0.05; fold change >2) were detected, including 56 up-regulated and 85 down-regulated. Among them, hsa_circ_0005565 stood out, for it had the highest fold change and was significantly increased in HF patients in quantitative real-time polymerase chain reaction validation. The top highly expressed EAT circRNAs corresponded to genes involved in cell proliferation and inflammatory response, including GSE1, RHOBTB3, HIPK3, UBXN7, PCMTD1, N4BP2L2, CFLAR, EPB41L2, FCHO2, FNDC3B, and SPECC1. The top enriched Gene Ontology term and Kyoto Encyclopedia of Genes and Genomes pathway were positive regulation of metabolic processes and insulin resistance, respectively.Conclusion:These data indicate EAT circRNAs may contribute to the pathogenesis of metabolic disorders causing HF.
简介:摘要目的观察肝细胞癌患者血清中微小RNA(miRNA,miR)-432、微小RNA-432(miR-30b)及微小RNA-432(miR-764)水平。方法选取安徽医科大学第三附属医院2015年1月30日至2018年1月30日收治的150例肝细胞癌患者,同时选取150例年龄匹配的体检结果健康者作为对照组,采用实时荧光定量聚合酶链反应(PCR)法检测研究对象外周血中miR-432、miR-30b及miR-764表达水平。观察miR-432、miR-30b及miR-764与肝细胞癌患者临床病理因素的相关性,并对肝细胞癌患者进行随访,观察miR-432、miR-30b及miR-764与患者总生存期(OS)的相关性。采用独立样本t检验及Log-rank检验。结果肝细胞癌患者外周血中miR-432(2.11±0.71)、miR-30b(1.88±0.68)及miR-764(1.90±0.65)水平均较对照组高(1.12±0.40、1.01±0.38、0.99±0.35,t=4.879、13.679、15.097,P<0.01)。miR-432、miR-764表达量与肝细胞癌TNM分期有相关(P<0.05),miR-30b与肝细胞癌TNM分期及分化程度有相关(P<0.05)。Kaplan-Meier法及Log-rank检验显示,miR-432、miR-30b及miR-764表达量升高组OS短于降低组(Log-rank χ2=16.433、10.575、7.998,P<0.05)。Cox多因素分析均显示,TNM分期、miR-432、miR-30b、miR-764、肿瘤分化程度是肝细胞癌OS的独立影响因素[比值比(OR)=2.904、2.135、1.651、1.496、1.205,P<0.05]。结论肝细胞癌患者循环中miR-432、miR-30b及miR-764表达上调,且与患者总生存率降低密切相关。
简介:AbstractThe present pandemic has posed a crisis to the economy of the world and the health sector. Therefore, the race to expand research to understand some good molecular targets for vaccine and therapeutic development for SARS-CoV-2 is inevitable. The newly discovered coronavirus 2019 (COVID-19) is a positive sense, single-stranded RNA, and enveloped virus, assigned to the beta CoV genus. The virus (SARS-CoV-2) is more infectious than the previously detected coronaviruses (MERS and SARS). Findings from many studies have revealed that S protein and RdRp are good targets for drug repositioning, novel therapeutic development (antibodies and small molecule drugs), and vaccine discovery. Therapeutics such as chloroquine, convalescent plasma, monoclonal antibodies, spike binding peptides, and small molecules could alter the ability of S protein to bind to the ACE-2 receptor, and drugs such as remdesivir (targeting SARS-CoV-2 RdRp), favipir, and emetine could prevent SASR-CoV-2 RNA synthesis. The novel vaccines such as mRNA1273 (Moderna), 3LNP-mRNAs (Pfizer/BioNTech), and ChAdOx1-S (University of Oxford/Astra Zeneca) targeting S protein have proven to be effective in combating the present pandemic. Further exploration of the potential of S protein and RdRp is crucial in fighting the present pandemic.
简介:摘要环状RNA(circular RNA, circRNA)是一类最新发现的非编码RNA,因具有特殊结构及可以在疾病中发挥调控作用而成为最近的研究热点。许多研究表明circRNA与心力衰竭的病理生理机制密切相关,特别是在心力衰竭中的关键环节——心脏重塑,circRNA表现出调控甚至是逆转心脏重塑的巨大潜力。文章对circRNA的功能及其在心力衰竭进展中的作用进行综述,并从心脏重塑3个重要环节(心肌细胞改变、心肌间质纤维化、血管再生)总结circRNA发挥的调控作用,总结目前circRNA在心力衰竭方面作为生物标志物的研究进展,为开发新的治疗靶标和生物标志物提供新思路。
简介:AbstractAlthough whole-exome sequencing and whole-genome sequencing has tremendously improved our understanding of the genetic etiology of human disorders, about half of the patients still do not receive a molecular diagnosis. The high fraction of variants with uncertain significance and the challenges of interpretation of noncoding variants have urged scientists to implement RNA sequencing (RNA-seq) in the diagnostic approach as a high throughput assay to complement genomic data with functional evidence. RNA-seq data can be used to identify aberrantly spliced genes, detect allele-specific expression, and identify gene expression outliers. Amongst eight studies utilizing RNA-seq, a mean diagnostic uplift of 15% has been reported. Here, we provide an overview of how RNA-seq has been implemented to aid in identifying the causal variants of Mendelian disorders.