Identification of Functional Genes in Pterygium Based on Bioinformatics Analysis.

Identification of Functional Genes in Pterygium Based on Bioinformatics Analysis.
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基于生物信息学分析的翼状胬肉功能基因鉴定

DOI:
10.1155/2020/2383516
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发表时间:
2020
影响因子:
--
通讯作者:
Zheng F
Zheng F
中科院分区:
生物学3区
文献类型:
--
作者:
Xu Y;Qiao C;He S;Lu C;Dong S;Wu X;Yan M;Zheng F

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竞争性内源性RNA(ceRNA)网络调控在许多疾病的发生、发展中起着重要作用。本研究旨在鉴定翼状胬肉中ceRNA网络的关键RNA,并探讨其分子机制。 差异表达的长非编码RNA(lncRNA)、微小RNA(miRNA)和mRNA从基因表达综合数据库(GEO)获得,并用R编程语言进行分析。提取LncRNA和miRNA表达,并通过GEO数据库合并,并与已发表的文献进行比较。lncRNA-miRNA-mRNA网络由选定的lncRNA、miRNA和mRNA构建。Metascape用于对ceRNA网络的mRNA进行基因本体论(GO)和京都基因和基因组百科全书(KEGG)分析,并在String网站上进行蛋白质-蛋白质相互作用(PPI)网络分析,以找到候选中心基因。比较毒理基因组学数据库(CTD)用于寻找与翼状胬肉密切相关的枢纽基因。采用逆转录-实时荧光定量PCR(RT-qPCR)方法验证hub基因的差异表达。 有8个lncRNA、12个miRNA和94个mRNA被过滤以构建初级ceRNA网络。选择排名前1个节点度的关键lncRNA LIN 00472来重建LIN 00472网络。GO和KEGG途径富集显示ceRNA网络中的mRNA主要参与嗜同性细胞通过质膜粘附分子的粘附、发育生长、神经元投射发育的调节、细胞成熟、突触组装、中枢神经系统神经元分化和PID FOXM 1途径。根据LINC 00472网络中mRNA的蛋白质-蛋白质相互作用网络(PPI)分析,根据节点度排序确定了10个候选枢纽基因。利用CTD数据库,我们鉴定了8个与翼状胬肉密切相关的hub基因,RT-qPCR证实其中6个hub基因在翼状胬肉中高表达。 我们的研究发现LINC 00472可能调控8个hub miRNAs(miR-29 b-3 p、miR-183- 5 p、miR-138- 5 p、miR-211- 5 p、miR-221- 3 p、miR-218- 5 p、miR-642 a-5 p、miR-5000- 3 p)和6个枢纽基因在翼状胬肉的发生发展过程中,主要通过PID FOXM 1途径参与ceRNA网络中的CDH 2、MYC、CCNB 1、ERBB 4、RB 1的表达。
The competing endogenous RNA (ceRNA) network regulatory has been investigated in the occurrence and development of many diseases. This research aimed at identifying the key RNAs of ceRNA network in pterygium and exploring the underlying molecular mechanism. Differentially expressed long noncoding RNAs (lncRNAs), microRNAs (miRNAs), and mRNAs were obtained from the Gene Expression Omnibus (GEO) database and analyzed with the R programming language. LncRNA and miRNA expressions were extracted and pooled by the GEO database and compared with those in published literature. The lncRNA-miRNA-mRNA network was constructed of selected lncRNAs, miRNAs, and mRNAs. Metascape was used to perform Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses on mRNAs of the ceRNA network and to perform Protein-Protein Interaction (PPI) Network analysis on the String website to find candidate hub genes. The Comparative Toxicogenomic Database (CTD) was used to find hub genes closely related to pterygium. The differential expressions of hub genes were verified using the reverse transcription-real-time fluorescent quantitative PCR (RT-qPCR). There were 8 lncRNAs, 12 miRNAs, and 94 mRNAs filtered to construct the primary ceRNA network. A key lncRNA LIN00472 ranking the top 1 node degree was selected to reconstruct the LIN00472 network. The GO and KEGG pathway enrichment showed the mRNAs in ceRNA networks mainly involved in homophilic cell adhesion via plasma membrane adhesion molecules, developmental growth, regulation of neuron projection development, cell maturation, synapse assembly, central nervous system neuron differentiation, and PID FOXM1 PATHWAY. According to the Protein-Protein Interaction Network (PPI) analysis on mRNAs in LINC00472 network, 10 candidate hub genes were identified according to node degree ranking. Using the CTD database, we identified 8 hub genes closely related to pterygium; RT-qPCR verified 6 of them were highly expressed in pterygium. Our research found LINC00472 might regulate 8 hub miRNAs (miR-29b-3p, miR-183-5p, miR-138-5p, miR-211-5p, miR-221-3p, miR-218-5p, miR-642a-5p, miR-5000-3p) and 6 hub genes (CDH2, MYC, CCNB1, RELN, ERBB4, RB1) in the ceRNA network through mainly PID FOXM1 PATHWAY and play an important role in the development of pterygium.
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