microRNAs在口腔扁平苔藓组织中的表达谱分析及3种miRNA的血清学表达  

The expression profile analysis of microRNAs in oral lichen planus tissues and the serological expression of three miRNAs

作　　者：张晋弘[1] 李天翠 吴景景[2] 姚曼曼 许彦枝[2] 刘健[2] ZHANG Jin-hong;LI Tian-cui;WU Jing-jing;YAO Man-man;XU Yan-zhi;LIU Jian(Department of Stomatology,the First Hospital of Hebei Medical University,Shijiazhuang 050030,China;Department of Stomatology,the Fourth Hospital of Hebei Medical University,Shijiazhuang 050011,China)

机构地区：[1]河北医科大学第一医院口腔科,河北石家庄050030 [2]河北医科大学第四医院口腔科,河北石家庄050011

出　　处：《河北医科大学学报》2023年第11期1260-1266,共7页Journal of Hebei Medical University

摘　　要：目的已有研究显示微小RNA(microRNAs,miRNAs)在口腔扁平苔藓(oral lichen planus,OLP)免疫调节中发挥重要作用,本研究的目的是获得OLP中miRNAs的表达谱,探讨miRNAs在OLP发病过程中可能发挥的作用,及其是否可作为OLP潜在的诊断标志物。方法收集3例病理学确诊的OLP病变组织(测序OLP组)和3例正常口腔黏膜(测序对照组),通过Illumina高通量测序筛选2组中差异表达的miRNAs。选择3个差异倍数大且表达丰度高的miRNAs进行靶基因预测和功能富集分析。纳入30例OLP患者(验证OLP组)和20例健康志愿者(验证对照组),用实时定量PCR(real-time quantitiy PCR,RT-qPCR)检测血清中3种miRNA的表达水平,再将验证OLP组分为糜烂组(20例)和非糜烂组(10例),分析3种miRNA的表达与OLP严重程度的关系。Pearson相关性系数分析三者表达的相关性,ROC曲线分析三者对OLP的诊断价值。结果应用DESeq软件,筛选出2组间差异表达的miRNAs共61个,其中表达上调的23个,下调的38个。利用Miranda数据库预测miR-142-3p、miR-146a-5p和miR-150-5p共同作用的靶基因87个(LIMD1、MOB1B、TEAD1等),GO分析显示这些靶基因与细胞间连接成分、信号传递密切相关,KEGG分析显示这些靶基因在Hippo信号通路上显著富集。与测序结果一致,验证OLP组血清中miR-142-3p、miR-146a-5p和miR-150-5p的表达均高于验证对照组(P<0.05)。将验证OLP组进一步分成糜烂组与非糜烂组,非糜烂组miR-146a-5p、miR-150-5p表达水平均高于验证对照组,差异有统计学意义(P<0.05),2组miR-142-3p的表达水平比较差异无统计学意义(P>0.05);糜烂组的miR-142-3p、miR-146a-5p和miR-150-5p的表达水平均高于验证对照组(P<0.05);糜烂组与非糜烂组间的3种miRNA的表达水平比较差异均无统计学意义(P>0.05),Pearson分析显示3种miRNA血清表达水平两两之间呈高度正相关(r=0.865、0.822、0.875,P<0.05)。ROC曲线分析显示,血清miR-142-3p、miR-146a-5p和miR-150-5p独Objective It has been found that microRNAs(miRNAs)play an important role in immune regulation of oral lichen planus(OLP).This study aimed to obtain the expression profile of miRNAs in OLP and to explore the possible role of miRNAs in the pathogenesis of OLP and whether they can be used as potential diagnostic markers of OLP.Methods Three pathologically confirmed OLP lesions(sequencing OLP group)and three normal oral mucosa(sequencing control group)were collected.The differentially expressed miRNAs between two groups were screened by Illumina high-throughput sequencing.Three miRNAs with large differential multiples and high expression abundance were selected for target gene prediction and functional enrichment analysis.Moreover,30 patients with OLP(validation OLP group)and 20 healthy volunteers(validation control group)were recruited.The expression levels of three miRNAs in serum were detected by real-time quantitative PCR(RT-PCR).Then validation OLP group was divided into erosion group(n=20)and non-erosion group(n=10).The relationship between the expression of three miRNAs and the severity of OLP was analyzed.Pearson correlation coefficient was used to analyze the correlation of the three miRNAs,and receiver operating characteristic(ROC)curve was used to analyze the diagnostic value of the three in OLP.Results A total of 61 differentially expressed miRNAs between two groups were screened by DESeq software,including 23 up-regulated and 38 down-regulated miRNAs.Eighty-seven target genes(LIMD1,MOB1B,and TEAD1)co-acted by miR-142-3p,miR-146a-5p and miR-150-5p were predicted by Miranda database.Gene ontology(GO)analysis showed that these target genes were closely related to intercellular connectivity components and signal transmission.Kyoto Encyclopedia of Genes and Genomes(KEGG)analysis showed that these target genes were significantly enriched in the Hippo signaling pathway.Consistent with the sequencing results,the expressions of miR-142-3p,miR-146a-5p and miR-150-5p in the validation OLP group were higher than tho

关 键 词：扁平苔癣 口腔 高通量测序 微小RNA 

分 类 号：R781.5[医药卫生—口腔医学]