NSCL/P患儿异常表达miRNAs的生物信息学分析

目的：：利用芯片杂交技术筛选出非综合征性唇腭裂( NSCL/P)患儿组织中异常表达的microRNAs ( miRNAs),并进行系统的生物信息学分析,预测其参与的生物学过程及信号通路。方法：收集4例健康新生儿的脐带组织和4例2岁以内NSCL/P患儿唇腭组织,分别进行miRNAs芯片杂交的比对研究,筛选出异常表达miRNAs,并将其分别通过TARGETSCAN-VERT、MIRDB和RNA22-HSA 3个数据库进行生物信息学预测并取交集得到靶基因,进行基因功能富集分析( gene ontology)和生物通路富集分析( pathway enrichment)。结果：样本中检测出异常表达的miRNAs 254条(上调表达181条,下调表达73条, P<0.05)。对异常表达的miRNAs进行生物信息学预测并取交集得到靶基因5029个。异常表达的miRNAs靶基因富集于解剖结构的发育、细胞黏附、细胞凋亡、细胞分化和细胞迁移等多个生物学过程；异常表达的miRNAs靶基因信号通路富集于Wnt、 mTOR、cGMP-PKG、TGFβ、PI3K-Akt等信号通路。结论：NSCL/P异常表达miRNAs预测出的靶基因富集于多个信号通路和生物学功能,其相关信号通路与生物学功能提示基因与环境因素能够影响NSCL/P的形成。

Bioinformatics analysis of dysregulated miRNAs in the tissue of children with nonsyndromic cleft lip and/or cleft palate

Objective:To screen the differentially expressed miRNAs in umbilical cord tissue of children with nonsyndromic cleft lip and/or cleft palate( NSCL/P) using miRNA microarray and comprehensive bioinformatics analysis for the prediction of related the bio-logical process and signaling pathways. Methods:Umbilical cord tissues of 4 cases of healthy newborns' and 4 lip or palate tissues of 4 cases with NSCL/P without other disease aged younger than 2 years were collected. The differentially expressed miRNAs were screened by miRNA microarray. Targets of dysrugulated miRNAs were predicted by TARGETSCAN-VERT, MIRDB and RNA22-HSA. All the gene sets were analyzed by gene ontology and pathway enrichment. Results: MiRNA microarray demonstrated that 254 miRNAs were dysregulated(181 miRNAs were up-regulated and 73 downregulated,P <0. 05). The dysregulated miRNAs targets contained 5029 genes. The dysregulated miRNAs targets were enriched in anatomical structure development,cell adhesion,cell proliferation,cell motili-ty and other biological processes. The dysregulated miRNAs targets were enriched in Wnt, mTOR, cGMP-PKG, TGFβ, PI3K-Akt and other signaling pathways. Conclusion:The target genes set of miRNAs are enriched in multiple biological processes and signaling path-ways related to NSCL/P, which indicate that genetic and environmental factors may influence the development process of NSCL/P.