简介:MicroRNA简称为miRNA,通常长度为19~25个核苷酸,是一类重要高度保守的非编码的小分子单链RNA。最新有关研究表明:miRNA与肿瘤存在着紧密关联,已在miRNA和肿瘤的发生、诊断及治疗等研究领域取得了一系列进展。本文从miRNA的概念与特征、miRNA的产生、作用机制及与肿瘤的关系等方面作一阐述。1miRNA的发现及其生物学特性1993年,Lee等[1]在秀丽新小杆线虫(C.elegans)中发现了第一个定时调控胚胎后期发育的基因lin-4,随后在多种生物物种中鉴别出上千种miRNAs[2-3]。许多miRNA的表达水平具有较强的保守性、基因簇集现象、时空特异性及组织特异性:①保守性。在已克隆到的miRNA中,几乎所有的miRNAs的基因存在于相近动物中,例如,C.elegans中多于1/3的miRNAs与人类同源[4]。②基因簇集现象。目前已知miRNA基因簇现象在果蝇中广泛存在,有超过一半的miRNAs是簇集的[5]。③时空特异性。目前研究较清楚的lin-4与let-7呈时间特异性表达。在C.elegans中,lin-4只在幼虫的第一期和第二期存...
简介:摘要MicroRNAs已经成为一种重要的调节脂质代谢的因子。最近发现的microRNA-33aandb(miR-33a/b)在体内胆固醇和脂肪酸代谢动态平衡中起着很重要的调节作用。这些microRNA嵌入在固醇响应元件结合蛋白基因(SREBF2和SREBF1)中,通过抑制参与到胆固醇输出和脂肪酸氧化的基因,比如ABCA1,CROT,CPT1,HADHB和PRKAA1,转录后调节胆固醇和脂肪酸代谢。miR-33a/b促进细胞内脂质沉积。在新近的动物实验研究中表明抑制这些小干扰RNA对脂蛋白代谢的调节有很显著的影响,包括增加血浆中高密度脂蛋白(HDL)和减少极低密度脂蛋白(VLDL)中甘油三酯的代谢。这些新的发现支持了microRNA拮抗剂在治疗血脂异常、动脉粥样硬化和相关代谢疾病中的潜在作用。
简介:AbstractPreoperative neoadjuvant chemoradiotherapy, combined with total mesorectal excision, has become the standard treatment for advanced localized rectal cancer (RC). However, the biological complexity and heterogeneity of tumors may contribute to cancer recurrence and metastasis in patients with radiotherapy-resistant RC. The identification of factors leading to radioresistance and markers of radiosensitivity is critical to identify responsive patients and improve radiotherapy outcomes. MicroRNAs (miRNAs) are small, endogenous, and noncoding RNAs that affect various cellular and molecular targets. miRNAs have been shown to play important roles in multiple biological processes associated with RC. In this review, we summarized the signaling pathways of miRNAs, including apoptosis, autophagy, the cell cycle, DNA damage repair, proliferation, and metastasis during radiotherapy in patients with RC. Also, we evaluated the potential role of miRNAs as radiotherapeutic biomarkers for RC.
简介:Objective:Puremucinousbreastcarcinoma(PMBC)isanuncommonhistologicaltypeofbreastcancercharacterizedbyalargeamountofmucinproduction.MicroRNA(miRNA)isalargeclassofsmallnoncodingRNAofabout22ntinvolvedintheregulationofvariousbiologicalprocesses.ThisstudyaimstoidentifythemiRNAexpressionprofileinPMBC.Methods:MiRNAexpressionprofilesin11PMBCswereanalyzedbymiRNA-microarrayandreal-timepolymerasechainreaction(PCR).Thirty-onePMBCsand27invasiveductalcarcinomaofnospecialtypes(IDC-NSTs)wereassessedbyimmunohistochemistryusingantibodiesagainstER,PR-progesteronereceptor,HER2,Ki-67,Bcl-2,p53,PCNA,andCK5and6.Results:WeanalyzedthemiRNAexpressionin11PMBCsandcorrespondingnormaltissuesusingmiRNA-microarrayandreal-timePCR,andfoundthatmiR-143andmiR-224-5pweresignificantlydownregulatedinmucinouscarcinomatissue.ComparedwithIDC-NSTs,PMBCshowedasignificantlyhigherERpositiverate,lowerHER-2positiverate,andlowercellproliferationrates.Conclusions:Toourknowledge,thisisthefirststudytodemonstratethemiRNAexpressionprofileofPMBC,andourfindingsmayleadtofurtherunderstandingofthistypeofbreastcancer.
简介:摘要目的分析不同分期及分级膀胱癌肿瘤组织中microRNA-21(miR-21)及microRNA-205(miR-205)表达量差异。方法将2014年1月至2014年12月间就诊的138例膀胱癌患者作为观察对象,根据病理分期,将患者分为T1期的A组(46例)、T2期的B组(34例)、T3期的C组(34例)及T4期的D组(24例),对比四组间miR-21及miR-205表达量差异;并根据病理分级,将患者分为低级组(88例)及高级组(50例),对比两组间miR-21及miR-205表达量差异。结果病理分期四组间,A组miR-21相对表达量最低,miR-205相对表达量最高,而D组miR-21相对表达量最高,miR-205相对表达量最低(P<0.05)。而病理分级两组间,低级组miR-21相对表达量明显最低高级组,miR-205相对表达量明显低于高级组(P<0.05)。结论不同分期及分级膀胱癌肿瘤组织中miR-21及miR-205表达量存在显著的差异。
简介:ObjectiveTocharacterizemicroRNA(miRNA)expressionprofileinmicrodissectedauditoryepitheliafromtheCorti'sOrganinnewbornandadultrats.MethodsTheTaqManMicroRNAArrayswereusedtoidentifyexpressionofmicroRNAinthenewbornandadultgroups.GOanalysiswasappliedtoanalyzethemainfunctionofthedifferentialexpressiongenesaccordingtotheGeneOntologywhichisthekeyfunctionalclassificationofNCBI.Similarly,PathwayanalysiswasusedtofindoutthesignificantpathwayofthedifferentialgenesaccordingtoKEGG,BiocartaandReatome.ResultsIncreasedexpressionwasseenin16miRNAsinmatureratcomparedtonewbornrats,withincreasedfoldingrangingfrom17to600folds.Expressionlevelsin2miRNAswerereducedinmaturerats,namelyrno-miR-29candrno-miR-29a.Thehigh-enrichmentGOstargetedbyover-expressedmiRNAswerenegativeregulationofepithelialcelldifferentiation,common-partnerSMADproteinphosphorylation,mesenchymal-epithelialcellsignaling,regulationoftransforminggrowthfactorbeta2production,etc.FunctionalanalysisofmiRNAsbyKEGGrevealedthat19signaltransductionpathwayswereupregulatedand14weredownregulated.ConclusionsThedifferenceinmiRNAexpressionpatternsintheorganofCortibetweenneonatalandadultratsmaybecloselyrelatedtomaturationoftheorganofCortiandlossofproliferativecapacityofinnerearhaircells,andTGFβsignalingmayplayanimportantroleinhaircellsregeneration.
简介:目的通过对结直肠癌患者血清进行实时定量PCR检测,筛选出结直肠癌转移相关的miRNA。方法通过文献检索,筛选出11个结直肠癌转移相关的miRNA(miRs-31,335,206,141,126,200b,200c,21,Let7a,Let7b和Let7c),收集2007年7月至2013年4月北京友谊医院收治的术前留置血清的结直肠癌转移(IV期)病例共计108例,其中结直肠肝转移患者72例,其他脏器转移患者36例;并纳入2008年1月至2010年6月术前留置血清的局灶性结直肠癌(L-CRC)(I-III期)病例共计116例作为对照组进行研究。通过对两组患者血清样本进行实时定量PCR检测结果找出结直肠癌转移相关miRNA。结果筛选出11个转移相关的miRNA中的7个miRNA(miRs-31、141、126、21、Let7a、Let7b和Let7c)可以从血清中被检测到。与局灶性结直肠癌患者相比,miR-141,miR-126,Let-7a和miR-21在转移性结直肠癌患者的血清中表达具有显著性差异(P〈0.0001,P〈0.0001,P=0.0120和P〈0.0001),可以作为结直肠癌转移相关miRNA。结论7个转移相关MiRNAs:miRs-31、141、126、21、Let7a、Let7b和Let7c可以从结直肠癌患者血清中被检测到;miR-141,miR-126,Let-7a和miR-21可以作为结直肠癌转移相关miRNA。
简介:MicroRNAs(miRNAs)aredynamicallyregulatedduringneurodevelopment,yetfewreportshaveexaminedtheirroleinspinabifida.Inthisstudy,weusedanestablishedfetalratmodelofspinabifidainducedbyintragastricallyadministeringoliveoil-containingall-transretinoicacidtodamsonday10ofpregnancy.Damsthatreceivedintragastricadministrationofall-transretinoicacid-freeoliveoilservedascontrols.ThemiRNAexpressionprofileintheamnioticfluidofratsat20daysofpregnancywasanalyzedusinganmiRNAmicroarrayassay.Comparedwiththatincontrolfetuses,theexpressionofmiRNA-9,miRNA-124a,andmiRNA-138wassignificantlydecreased(>2-fold),whereastheexpressionofmiRNA-134wassignificantlyincreased(>4-fold)intheamnioticfluidofratswithfetusesmodelingspinabifida.Theseresultswerevalidatedusingreal-timequantitativereverse-transcriptionpolymerasechainreaction.HierarchicalclusteringanalysisofthemicroarraydatashowedthatthesedifferentiallyexpressedmiRNAscoulddistinguishfetusesmodelingspinabifidafromcontrolfetuses.OurbioinformaticsanalysissuggestedthatthesedifferentiallyexpressedmiRNAswereassociatedwithmanycytologicalpathways,includinganervoussystemdevelopmentsignalingpathway.ThesefindingsindicatethatfurtherstudiesarewarrantedexaminingtheroleofmiRNAsthroughtheirregulationofavarietyofcellfunctionalpathwaysinthepathogenesisofspinabifida.Suchstudiesmayprovidenoveltargetsfortheearlydiagnosisandtreatmentofspinabifida.
简介:Receptortyrosinekinases(RTKs)suchastheepidermalgrowthfactorreceptor(EGFR)regulatecellularhomeostaticprocesses.EGFRactivatesdownstreamsignalingcascadesthatpromotetumorcellsurvival,proliferationandmigration.DysregulationofEGFRsignalingasaconsequenceofoverexpression,amplificationandmutationoftheEGFRgeneoccursfrequentlyinseveraltypesofcancersandmanybecomedependentonEGFRsignalingtomaintaintheirmalignantphenotypes.Consequently,concertedeffortshavebeenmountedtodeveloptherapeuticagentsandstrategiestoeffectivelyinhibitEGFR.However,limitedtherapeuticbenefitstocancerpatientshavebeenderivedfromEGFR-targetedtherapies.Awell-documentedobstacletoimprovedpatientsurvivalisthepresenceofEGFR-inhibitorresistanttumorcellvariantswithinheterogeneoustumorcellmasses.Here,wesummarizethemechanismsbywhichtumorsresistEGFR-targetedtherapiesandhighlighttheemergingroleofmicroRNAs(miRs)asdownstreameffectormoleculesutilizedbyEGFRtopromotetumorinitiation,progressionandthatplayaroleinresistancetoEGFRinhibitors.WealsoexamineevidencesupportingtheutilityofmiRsaspredictorsofresponsetotargetedtherapiesandnoveltherapeuticagentstocircumventEGFR-inhibitorresistancemechanisms.
简介:AbstractIn recent years, an increasing number of young women have been diagnosed with cancer, including some nulliparous women. Therefore, many young patients with early-stage cancer desire to preserve fertility after cytotoxic oncological treatments. It is important to develop a multidisciplinary approach to achieve the best outcomes for each patient. On the other hand, there has been a sharp increase in microRNAs (miRNAs) as potential biomarkers for the diagnosis, prognosis, and evaluation of treatment efficacy of several diseases. MiR-543 has been reported to affect the pathogenesis and progression of diseases via complex mechanisms. Understanding the regulatory role of miR-543 may aid comprehension of the pathogenesis and treatment of a broad range of diseases. Therefore, we provide an overview of the biogenesis, function, and role of miR-543 in various systems. These results shed light on the anticancer and endometrial protection role of miR-543 in young patients with gynecologic tumors and highlight the clinical potential of miR-543-based applications and related challenges.
简介:摘要角膜新生血管可继发于多种眼部疾病,是影响角膜透明度的主要原因之一。微小RNA(microRNA, miRNA)与病理性角膜新生血管密切相关,可通过调控多种细胞因子的表达和信号传导途径影响角膜新生血管生成。抑制角膜新生血管的miRNA包括miR-184、miR-204,促进角膜新生血管的miRNA包括miR-126、miR-132、miR-21和miR-27a/b。调控这些miRNA有望成为角膜新生血管的治疗方法。对促进角膜血管新生的miRNA,可使用反义miRNA寡核苷酸antagomir抑制内源性miRNA作用。(国际眼科纵览,2020, 44: 192-196)
简介:Epithelialovariancancer(EOC)istheleadingcauseofdeathamongallgynecologicalmalignancies.Despitethetechnologicalandmedicaladvancesoverthepastfourdecades,suchasthedevelopmentofseveralbiologicalmarkers(mRNAandproteinsbiomarkers),themortalityrateofovariancancerremainsachallengebecauseofitslatediagnosis,whichisspecificallyattributedtolowspecificitiesandsensitivities.Underthiscompulsivescenario,recentadvancesinexpressionbiologyhaveshiftedinidentifyinganddevelopingspecificandsensitivebiomarkers,suchasmicroRNAs(miRNAs)forcancerdiagnosisandprognosis.MiRNAsareanovelclassofsmallnon-codingRNAsthatderegulategeneexpressionattheposttranscriptionallevel,eitherbytranslationalrepressionorbymRNAdegradation.Thesemechanismsmaybeinvolvedinacomplexcascadeofcellulareventsassociatedwiththepathophysiologyofmanytypesofcancer.MiRNAsareeasilydetectableintissueandbloodsamplesofcancerpatients.Therefore,miRNAsholdgoodpromiseaspotentialbiomarkersinovariancancer.Inthisreview,weattemptedtoprovideacomprehensiveprofileofkeymiRNAsinvolvedinovariancarcinomatoestablishmiRNAsasmorereliablenon-invasiveclinicalbiomarkersforearlydetectionofovariancancercomparedwithproteinandDNAbiomarkers.