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  • 简介:文昌鱼最近是现存的种到脊椎动物的祖先。文昌鱼的分发将为脊椎动物的进化研究借给一些提示的microRNA(miRNA)的观察。在这研究,使用佛罗里达文昌鱼(Branchiostomafloridae)的公开可得到的支架数据染色体,我们屏蔽了并且描绘在另外的种类被识别了的miRNAs的相当或相同的事物。总共,68个如此的相当或相同的事物被获得并且分类家庭进33。大多数这些miRNAs在染色体作为簇被散布。内部种类的比较证明许多miRNAs,以前作为脊椎动物特定或哺乳动物特定被认为,也是在文昌鱼的现在,当以前被看作了protostome特定的某miRNAs也在文昌鱼存在时。与ciona相比,文昌鱼有明显的miRNA基因扩大,但是种系发生的分析证明文昌鱼的复制miRNAs或簇在脊椎动物比那些复制的有更高的相同水平。

  • 标签:动物进化文昌鱼小分子RNAmiRNA脊椎动物表征
  • 简介:RecentstudiesrevealingtheimportantrolesofmicroRNAs(miRNAs)inregulatingexpressionofionchannelgeneshaveopeneduparesearchfieldforextendinganddeepeningourinvesti-gationintothecardiacexcitabilityandtheassociatedarrhythmogenesis.Cardiacexcitability,thefundamentalpropertyofthecardiacmyocytes,definesthecardiacconduction,repolarization,automaticity,intracellularcalciumhandling,andtheirregionalheterogeneity.OurpreviousandongoingstudiesandtheworkfromotherlaboratorieshavedemonstratedthesignificantinvolvementofmiRNAsinregulatingeveryaspectsofcardiacexcitability.Wehavefoundearlierthatthemuscle-specificmiRNAmiR-1boostsupthearrhythmogenicpotentialthroughtargetinggapjunctionchannelconnexin43inmyocardialinfarction.AsubsequentstudyrevealedthatmiR-1canalsocausearrhythmiasbyimpairingCa2+handlingbytargetingphosphatase.Wethenidentifiedanothermuscle-specificmiRNAmiR-133promotesabnormalQTprolongationbyrepressingHERGK+channelexpressionindiabeticcardiomyopathy.Subsequently,wediscoveredthatbothmiR-1andmiR-133areinvolvedinthereexpressionofpacemakerchannelsHCN2/HCN4toenhanceabnormalautomaticityincardiachypertrophy.Recently,wefurtheridentifiedmiR-328asanimportantdeterminantforatrialfibrillation(AF)andtheassociatedadverseatrialelectricalremodelingviatargetingL-typeCa2+channels.Whilealltheabove-mentionedmiRNAsareproarrhythmic,wehavenewlyidentifiedforthefirsttimeanaturalantiarrhythmicmiRNAmiR-26.WefoundthatallthreemembersofthemiR-26familyisdownregulatedintheirexpressioninAFtissuesandthisdownregulationincreasesAFvulnerabilityasaresultofremovalofanendogenousantiarrhythmicfactor.miR-26downregulationshortensatrialactionpotentialfavoringAFbyincreasinginwardrectifierK+current(IK1)density.ThisiscausedbyanupregulationofKir2.1K+channelsu

  • 标签:
  • 简介:MicroRNAs(miRNAs)aresmall,non-codingsingle-strandedRNAsthatcanmodulatetargetgeneexpressionatposttranscriptionallevelandparticipateincellproliferation,differentiation,andapoptosis.Tcellshaveimportantfunctionsinacquiredimmuneresponse;miRNAsregulatethisimmuneresponsebytargetingthemRNAsofgenesinvolvedinTcelldevelopment,proliferation,differentiation,andfunction.Forinstance,miR-181familymembersfunctioninprogressionbytargetingBcl2andCD69,amongothers.MiR-17tomiR-92clustersfunctionbybindingtoCREB1,PTEN,andBim.ConsideringthatthesuppressionofTcell-mediatedimmuneresponsesagainsttumorcellsisinvolvedincancerprogression,weshouldinvestigatethemechanismbywhichmiRNAregulatesTcellstodevelopnewapproachesforcancertreatment.

  • 标签:microRNA调节性T细胞调控机制细胞免疫反应miRNA癌症治疗
  • 简介:AbstractPancreatic cancer is one of the most aggressive malignancies. The poor prognosis of pancreatic cancer patients is mainly attributed to low diagnostic rate at the early stage, highly aggressive nature coupled with the inadequate efficacy of current chemotherapeutic regimens. Novel therapeutic strategies are urgently needed for pancreatic cancer.MicroRNAs(miRNAs) play an important regulatory role in key processes of cancer development. The aberrant expression of miRNAs is often involved in the initiation, progression, and metastasis of pancreatic cancer. The discovery of tumor suppressor miRNAs provides prospects for the development of a novel treatment strategy for pancreatic cancer. We reviewed recent progress on the understanding of the role of miRNAs in pancreatic cancer, highlighted the efficient application of miRNAs-based therapies for pancreatic cancer in animal models and clinical trials, and proposed future prospects. This review focuses on the promise of integrating miRNAs into the treatment of pancreatic cancer and provides guidance for the development of precision medicine for pancreatic cancer.

  • 标签:Pancreatic cancerMicroRNAMicroRNA carriersPrecision medicine
  • 简介:心房颤动是临床上最常见的心律失常,其易感因素众多、发病机制主要为心房电重构和结构重构,但具体分子调控机制尚不明确。微小RNA(MicroRNAs)是一类长度为18-25个核苷酸的内源性非编码小RNA,可通过与靶基因mRNA3’非翻译区的不完全互补结合,在转录后水平抑制靶基因的表达。近年来研究发现microRNAs在心房颤动的发生发展过程中起到了重要作用。房颤相关的microRNAs主要包括miR-1、miR-26和miR-101,miR-133,miR-328、miR-21、miR-30等,主要通过调控离子通道的表达影响心房电重构,或通过调控心肌纤维化及细胞外基质沉积参与心房结构重构。

  • 标签:心房颤动MICRORNAS心房重构离子通道
  • 简介:BackgroundMicroRNAshaverecentlybeenconsideredasbiomarkersinseveraldifferentcardiovasculardiseases,however,sofartherearenocirculatingmiRNAsdataabouthypertension.Therefore,theaimofthepresentpilotstudywastoidentifycirculatingmiRNAsforhypertensionbiomarkers.MethodsUsinganAgilentmicroarray,plasmamiRNAswereprofiledfromplasmasamplesof10patientswithuntreatedessentialhypertensionand10healthycontrols.CandidatebiomarkersidentifiedintheprofilesweresubjectedtovalidationbyusingquantitativePCRinanindependentsamplesetof20patientswithuntreatedessentialhypertensionand20healthycontrols.Then,weassessedtheselectedmiRNAsforthedetectionanddiagnosisofhypertensionfromplasmasamplesof70patientswithuntreatedessentialhypertensionand20healthycontrols.TheSpearmancorrelationcoefficientwasusedtoassessedtheselectedmiRNAscorrelationswithbloodpressure.Theareaunderthereceiveroperatingcharacteristiccurve(AUC)wasusedtoevaluatediagnosticaccuracy.ResultsTheexpressionsofselected8miRNAswereinvestigatedindependentlyinplasmasamplesfrom10hypertensionpatientsand10healthysubjects.ThelevelsofcirculatingmiR-30c-5p,miR-133b,miR-29b-3p,miR-29a-3p,miR-29c-3p,miR-30a-3p,miR-let7b-3pexpressionweresignificantlydownregulatedinhypertensiongroupcomparedwithhealthygroupandthelevelofhsa-miR-92b-3pwassignificantlyunregulatedbetweenthegroups.WeusedqRT-PCRassaytoconfirmtheexpressionof8candidatemiRNAs,miR-30c-5p(P<0.001),miR-29b-3p(P<0.001),miR-29a-3p(P=0.027),miR-29c-3p(P<0.001),miR-92b-3p(P=0.003),miR-30a-3p(P=0.704),miR-133b(P=0.346),andmiR-let7b(P=0.161).ThediagnosticaccuracyofmiR-30c-5p,miR-29b-3p,miR-29a-3p,miR-29c-3pandmiR-92b-3p,asmeasuredbyAUC,were0.897,0.90,0.829,0.825and0.832,respectively,withallP<0.001.ConclusionsTheplasmalevelsofmiR-30c-5p,miR-29b-3p,miR-29a-3p,miR-29c-3pandmiR-92b-3passociatedwithhypertensionwhichprovideanimp

  • 标签:生物标志物高血压病microRNAMIRNAS高血压患者RT-PCR法
  • 简介:天生的免疫系统认识到通过编码germline的模式识别受体(PRR)入侵病原体,它得到天生的抗菌剂和煽动性的回答并且开始适应免疫控制或消除感染。像使用费的受体(TLR)和retinoic酸可诱导的基因(RIG-I)我是关键天生的有免疫力的PRR并且被精致的机制紧调整响应外国侵略者保证有益的结果。尽管许多在文学的焦点在发炎的蛋白质管理者的学习上,microRNAs(miRNAs)作为煽动性的过程的某些特征的重要控制器出现了。几miRNAs被TLR和RIG-I激活作为TLR并且RIG-I发信号的反馈管理者在myeloid房间和行为导致。在这评论,我们包括地讨论miRNA网络怎么对TLR并且RIG-I在煽动性的回答的开始和结束发信号和他们的角色作出回应的最近的理解。增加的证据也显示编码病毒的miRNAs和细胞的miRNAs在病毒的复制有重要功能并且招待抗病毒的豁免。

  • 标签:TLR小分子RNAToll样受体miRNA抗病毒免疫炎症反应
  • 简介:一、引言1993年Lee等[1]在线虫中首次发现microRNA(miRNA)-lin-4。2000年Reinhart等[2]再次在线虫中发现第二个miRNA即let-7。2004年Calin等[3]研究发现miR-15和miR-16与慢性B细胞淋巴瘤发生相关,首次揭示miRNA与癌症发生相关。随后掀起了一股miRNA研究热潮,通过检索Pubmed发现近年来miRNA相关文献迅速增加。现在已经证实miRNA的生物学功能非常广泛,它不仅参与细胞发育、组织生长分化、细胞代谢等多个方面,而且它的异常表达和调控参与人类很多疾病的发生。目前发现miRNA

  • 标签:细胞代谢MICRORNAS淋巴瘤胰腺Β细胞细胞发育脂肪分解
  • 简介:BackgroundMyocardialfibrosisplaysacriticalroleintheprocessofdiabeticcardiacremolding.MicroRNAs(miRNAs)areendogenous,smallnon-codingRNAsthatnegativelyregulategeneexpressionindiversebiologicalandpathologicalprocesses.However,therolesofmiRNAsinmyocardialfibrosishavenotbeenwellelucidated.Inthepresentstudy,miRNAsprofilesinthefibroticmyocardiumofdb/dbmiceandmiRNAsexpressioninTGF-β1-stimulatedmousecardiacmyofibroblastswasexamined.MethodsHeartfunctionof18-week-olddb/dbmiceanddb/mcontrolmicewasdetectedbyechocardiography.miRNAexpressionprofileindiabeticmyocardiumwasdetectedbymiRNAmicroarray.Quantitativereal-timePCRwasusedtodeterminetheexpressionoffibrosis-relatedgenesandmiRNAprecursorsofinterest.Westernblotwasusedtodetectthelevelsoffibrosis-relatedproteins,activatedSmad3andtotalSmad3.ResultsTheresultofechocardiographyshowedthatleftventricularsystolicanddiastolicfunctionwasimpairedin18-week-olddb/dbmicewithoutsignificantchangeofejectionfraction(EF)andfractionalshortening(FS).Fibrosis-relatedgenesexpressionwasupregulatedandtheamountofphosphorylatedSmad3wasincreasedsignificantlyinthediabeticmyocardium.miRNAsdysregulationwasshownindiabeticmyocardium,sixty-eightmiRNAs,includingmiR-208b,miR-29b,miR-26bandmiR-30e,wereincreasedovertwo-fold,meanwhile,sixty-twomiRNAsweredecreasedmorethantwo-foldinthemyocardiumofdb/dbmicecomparedtodb/mcontrols.InparallelwithasignificantupregulationofCol1a1,Col3a1andCTGFmiRNAexpression,miR-208b,miR-29b,miR-26bandmiR-30eprecursorswerealsoshowntobeupregulatedinTGF-β1-inducedC57bl/6mousecardiacmyofibroblasts.ConclusionsmicroRNAsweredysregulatedindiabeticmyocardium,withtheactivationofTGF-β/smad3pathway,contributingtodiabeticmyocardialfibrosis.

  • 标签:microRNA心肌纤维化小鼠模型糖尿病失调MIRNAS
  • 简介:MicroRNAs(miRNAs)是一类广泛存在于真核细胞中长约18~23个核苷酸的小分子非编码RNA,具有转录后基因调控的功能,参与调节细胞的分化、增殖、凋亡、迁移等多种生物学进程。现今乳腺癌已成为女性常见的恶性肿瘤之一,但其发病病因尚未完全清楚。近年来,通过对分子生物学的研究,发现miRNAs是一类潜在的强有力的评估乳腺癌的发生、发展,诊断、治疗及预后的生物学指标。本文主要对miRNAs这一类新的肿瘤分子生物学标记物在乳腺癌中的作用机制作一综述。

  • 标签:MIRNAS乳腺癌作用机制
  • 简介:AbstractMore evidences show thatmicroRNAsplay an important role in the pathogenesis of inflammation and autoimmune diseases including Lichen planus, and are an attractive therapeutic target. MicroRNA family plays an important role in the regulation of gene expression, which involves cell proliferation, apoptosis, growth, differentiation and metabolism, vascularization, immune response and other biological processes. The changes of expression profile and expression level are closely related to the occurrence and development of many diseases, such as tumor, inflammatory disease and autoimmune disease relevant. However, there are few reports on microRNA in the pathogenesis of LP. This review summarizes the research advance ofmicroRNAs(microRNAs-137,microRNAs-125b,microRNAs-138,microRNAs-27b,microRNAs-203) and their downstream proteins in LP.

  • 标签:lichen planuspathogenesismicroRNAs
  • 简介:摘要microRNA(miRNA)是一类长度约为22个核苷酸的非编码小分子RNA,主要参与基因转录后水平调控,它通过与靶mRNA完全或不完全的互补配对,促进目标mRNA降解或抑制蛋白翻译。近年来,大量与肿瘤发生相关的miRNA相继被发现,参与人类肿瘤形成的多条信号通路,同时提出miRNA可作为肿瘤治疗的潜在靶点。本文就miRNA在肿瘤研究方面所取得的最新进展作一综述。

  • 标签:miRNA微小RNA肿瘤发生肿瘤治疗
  • 简介:Seventy-fivepreviouslyknownplantmicroRNAs(miRNAs)wereclassifiedinto14familiesaccordingtotheirgenesequenceidentity.Atotalof18,694plantexpressedsequencetags(EST)werefoundintheGenBankESTdatabasesbycomparingallpreviouslyknownArabidopsismiRNAstoGenBank'splantESTdatabaseswithBLASTalgorithms.AfterremovingtheESTsequenceswithhighnumbers(morethan2)ofmismatchednucleotides,atotalof812ESTcontigswereidentified.AfterpredictingandscoringtheRNAsecondarystructureofthe812ESTsequencesusingmFoldsoftware,338newpotentialmiRNAswereidentifiedin60plantspecies,miRNAsarewidespread.SomemicroRNAsmayhighlyconserveintheplantkingdom,andtheymayhavethesameancestorinveryearlyevolution.ThereisnonucleotidesubstitutioninmostmiRNAsamongmanyplantspecies.SomeofthenewidentifiedpotentialmiRNAsmaybeinducedandregulatedbyenvironmentalbioticandabioticstresses.Somemaybepreferentiallyexpressedinspecifictissues,andareregulatedbydevelopmentalswitching.ThesefindingssuggestthatESTanalysisisagoodalternativestrategyforidentifyingnewmiRNAcandidates,theirtargets,andothergenes.AlargenumberofmiRNAsexistindifferentplantspeciesandplayimportantrolesinplantdevelopmentalswitchingandplantresponsestoenvironmentalabioticandbioticstressesaswellassignaltransduction.EnvironmentalstressesanddevelopmentalswitchingmaybethesignalsforsynthesisandregulationofmiRNAsinplants.AmodelformiRNAinductionandexpression,andgeneregulationbymiRNAishypothesized.

  • 标签:RNA植物环境胁迫基因表达表达序列标签鉴定
  • 简介:Ovariancancerisoneofthemostlethalmalignantgynecologicaltumors.Morethan70%ofpatientswithovariancancerarediagnosedatadvancedstage.The5-yearsurvivalinpatientswithadvancedovariancancerislessthan30%becauseofthelackofeffectivebiomarkersfordiagnosis,prognosis,andpersonalizedtreatment.MicroRNA(miR)isaclassofsmallnoncodingRNAsthatnegativelyregulategeneexpressionprimarilythroughpost-transcriptionalrepression.ManystudiesontissuemiRinovariancancerhavebeencarriedoutandshowgreatpotentialinclinicalpractice.However,tissuesamplesarenoteasilyavailablebecausesamplingcausesinjury.Researchershavestartedtofocusonplasma/serummiR,assumingthatbloodsamplesmayreplacetissuesamplesinmiRresearchinthefuture.Plasma/serummiRresearchisstillinitsearlystages.Studiesonitsfunctionintheearlydiagnosisofovariancancerhaveachievedsomeprogress,butplasma/serummiRprofilingforprognosisandpersonalizedtreatmentofovariancancerremainsunknown.Athoroughunderstandingofthefunctionofplasma/serummiRinovariancancerwillfacilitateearlydiagnosisandimprovetreatmentforovariancancer.

  • 标签:生物标志物microRNA诊断功能卵巢癌预后循环
  • 简介:AbstractEndometriosis (EM) is a benign gynecological disease that affects the fertility and health of women of reproductive age; it is characterized by the presence of endometrial glands and stroma outside the uterine cavity. Although several hypotheses have been proposed to explain the underlying cause of EM, its pathogenesis remains obscure. Recently, non-coding RNAs were reported to be involved in the occurrence and development of EM.MicroRNAsand long non-coding RNAs are the main members of the non-coding RNA family that contribute to EM progression in various aspects, such as cell proliferation, apoptosis, invasion, and angiogenesis. Angiogenesis plays a pivotal role in the initiation and development of EM and provides a substantial background for the invasion, proliferation, and long-term growth of endometriotic implants. This review aimed to investigate the role ofmicroRNAsand long non-coding RNAs in regulating angiogenesis in EM and discuss how this mechanism can be used for diagnostic and therapeutic purposes in EM.

  • 标签:MicroRNAsLong non-coding RNAsEndometriosisAngiogenesisPathogenesis
  • 简介:AbstractObjective:Laboratory diagnosis of neurosyphilis (NS) remains a great challenge. This study was the aimed to identify miRNA candidates as biomarkers to distinguish between NS, non-neurosyphilis, and healthy controls (HCs).Methods:We analyzed miRNA expression profiles in peripheral blood mononuclear cells (PBMCs) from six patients with NS, eight patients with secondary syphilis (SS), and five HCs using microarray technology. The differentially expressed miRNAs were validated in 33 NS samples, 31 SS samples, and 30 HC samples using TaqMan miRNA real-time qPCR (qRT-PCR).Results:Thirty-nine miRNAs were differentially expressed in SS and NS patients compared with HCs. Thirteen miRNAs were randomly selected to validate their expression levels in the same samples used in microarray assay by qRT-PCR. All miRNAs were upregulated in SS and NS samples compared with HC. qRT-PCR analysis of the expression of the 13 miRNAs in a second cohort (76 samples) showed that the average expression levels of nine miRNAs were higher in SS than in NS (SS: 0.185, NS: 0.136, P=3.8E-10), while the expressions of the other four miRNAs were lower in SS than in NS (SS: 0.000757, NS: 0.000873, P=0.022). ROC curve analysis of the 13 miRNAs showed the area under the curve value to be 1.00 for distinguishing SS patients from HCs, 1.00 for distinguishing NS patients from HCs, 1.00 for distinguishing SS and NS patients from HCs, and 0.968 for distinguishing NS from SS patients.Conclusion:The present study is the first one that identified differentially expressed miRNAs in PBMCs from patients with NS. Our results suggest that the 13 candidate miRNAs in PBMCs may be novel noninvasive biomarkers for NS diagnosis.

  • 标签:diagnosismicroRNAsneurosyphilisperipheral blood mononuclear cellssyphilis
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