萎缩性骨不连中miRNAs的异常表达与其靶基因的初步预测  

Abnormal expression of miRNAs in atrophic bone nonunion and preliminary prediction of the target genes

作　　者：魏均强[1] 张伯勋[1] 陈华[1] 唐佩福[1] 王岩[1] 陶笙[1] 梁雨田[1] 张群[1] 

机构地区：[1]中国人民解放军总医院骨科专科医院骨七病区,北京100853

出　　处：《中国骨肿瘤骨病》2010年第3期236-239,244,共5页Chinse Journal Of Bone Tumor And Bone Disease

基　　金：北京自然科学基金项目(编号:7083114)

摘　　要：目的筛选研究萎缩性骨不连断段修复组织中异常表达的microRNAs(miRNAs),并对其可能的功能性靶基因进行预测分析。方法以萎缩性骨不连患者断端瘢痕组织(A组,3例)与正常骨折愈合后内固定钢板取出时钢板周围的骨痂组织(B组,3例)作为研究对象,采用Exiqon miRCURY^(TM) LNA microRNA芯片(11.0版)进行筛选分析,比较A组组织中是否存在异常表达的miRNAs,并采用浏览计算机预测数据库等生物信息学的方法预测其可能的靶基因,探寻miRNAs可能参与的萎缩性骨不连相关病理生理过程。结果A组相对B组有9种miRNAs发生1.5倍以上表达上调(hsa-miR-149*,hsa-miR-221,hsa-miR-628-3p,hsa-miR-654-5p,以及5种hsa-miRPlus),9种miRNAs发生1.5倍以上表达下调(hsa-let-7b*,hsa-miR-220b,hsa-miR-513a-3p,hsa-miR-551a,hsa-miR-576-5p,hsa-miR-1236,kshv-miR-K12-6-5p,以及2种hsa-miRPlus)。生物信息学分析发现,表达异常的miRNAs与多数成骨基因存在作用靶点。结论萎缩性骨不连的断端修复组织存在miRNAs的异常表达,其靶基因包括BMP家族在内的众多成骨性基因。数种miRNAs,特别是4种上调的miRNAs(hsa-miR-149*、hsa-miR-221、hsa-miR-628-3p和hsa-miR-654-5p)有可能在调控骨折向不愈合发展中具有重要作用。Objective To screen and study the abnormal expression of microRNAs （miRNAs） in the scar tissues of atrophic bone nonunion, and to predict and analyze the functional target genes. Methods Two groups of patients were involved： group A （n=3） and group B （n=3）. Patients in group A sustained atrophic bone nonunion, and patients in group B demonstrated normal bone healing after fracture. We studied the scar tissues of atrophic bone nonunion in group A and the callus tissues around the steel plate after the internal fixation was removed in group B. Exiqon miRCURY LNATM microRNA microarraies （version 11.0） were used to screen miRNAs with abnormal expression in both groups. Through searching in gene-rlated databases, we tried to identify potential target genes of the miRNAs with abnormal expressions. Other bioinformatic methods were also used to predict the potential target genes, and to seek the pathophysiologic courses related to atrophic bone nonunion which miRNAs might be involved. Results Compared with the miRNAs expression in group B, the expression of 9 types of miRNAs in group A was up-regulated by more than 1.5 times of the normal level. The miRNAs were hsa-miR-149＊, hsa-miR-221, hsa-miR-628-3p, hsa-miR- 654-5p, and 5 types of hsa-miRPlus. While the expression of another 9 types of miRNAs was down-regulated more than 1.5 times of the normal level. They were hsa-let-7b＊, hsa-miR-220b, hsa-miR-513a-3p, hsa-miR-551 a, hsa-miR-576-5p, hsa-miR-1236, kshv-miR-K12-6-5p, and 2 types of hsa-miRNAs plus. Bioinformatics analysis revealed that there were many target points of miRNAs with abnormal expressions in a majority of osteoblastic genes. Conclusions Abnormal expression of miRNAs was found in the scar tissues of atrophic bone nonunion. The target genes include the family of bone morphogenetic protein （BMP） and many other osteoblastic genes. Some genes, especially the 4 up-regulated ones, hsa-miR-149＊, hsa-miR-221, hsa-miR-628-3p and hsa-miR-654-5p, might play an important role in causing bon

关 键 词：萎缩性骨不连 芯片 MIRNA 靶基因 调控 

分 类 号：R683[医药卫生—骨科学]