Chen Gang, Li Meng-Xue, Wang Heng-Xue, Hong Jia-Wei, Shen Jun-Yu, Wang Qi, Shi Qiao-Mei, Ge Xing, Ding Zhen, Zhang Jin-Peng, Xu Li-Chun
School of Public Health, Xuzhou Medical University, Xuzhou, 209 Tong-Shan Road, Xuzhou, Jiangsu, 221000, China.
School of Public Health, Xuzhou Medical University, Xuzhou, 209 Tong-Shan Road, Xuzhou, Jiangsu, 221000, China.
Int J Pediatr Otorhinolaryngol. 2018 Aug;111:128-137. doi: 10.1016/j.ijporl.2018.06.005. Epub 2018 Jun 7.
Cleft lip with or without cleft palate (CL/P) is one of the most common congenital defects, which etiology involves both genetic and environmental factors. Previous studies have shown that miR-199a-5p may mediate the occurrence of CL/P. However, the key target genes regulated by miR-199a-5p are not clear. In this study, we employed a systematic bioinformatics analysis of target genes regulated by miR-199a-5p which may be involved in CL/P.
The miRBase, Human miRNA tissue atlas, miRecords, miRpathDB, miRWalk, miRTarBase, DIANA-TarBase (v7.0), Literature search, DAVID software, Cytoscape plugin ClueGO + Cluepedia app, MalaCards, TargetScanhuman7.1, Venny 2.1, STRING and GEO databases were comprehensive employed to identify the key genes regulated by miR-199a-5p associated with CL/P.
Total 429 experimentally validated target genes were obtained from five miRNAs related databases. Expressions of miR-199a-5p and its experimentally validated target genes were elevated in bone, brain and skin. KEGG pathway analysis revealed that the target genes were enriched in focal adhesion, microRNAs in cancer and hippo signaling pathway. Biological process categorization revealed that significant portions of the target genes were grouped as transcription, DNA-templated. Total eight intersection genes were identified by using MalaCards and TargetScanhuman7.1. The target gene transforming growth factor alpha (TGFA) of miR-199a-5p involved in CL/P is screened and verified.
MiR-199a-5p may mediate CL/P by regulating key target gene TGFA. The study may contribute to a better understanding of the etiology of CL/P.
唇裂伴或不伴腭裂(CL/P)是最常见的先天性缺陷之一,其病因涉及遗传和环境因素。先前的研究表明,miR-199a-5p可能介导CL/P的发生。然而,miR-199a-5p调控的关键靶基因尚不清楚。在本研究中,我们对可能参与CL/P的miR-199a-5p调控的靶基因进行了系统的生物信息学分析。
综合利用miRBase、人类miRNA组织图谱、miRecords、miRpathDB、miRWalk、miRTarBase、DIANA-TarBase(v7.0)、文献检索、DAVID软件、Cytoscape插件ClueGO + Cluepedia应用程序、MalaCards、TargetScanhuman7.1、Venny 2.1、STRING和GEO数据库来鉴定与CL/P相关的miR-19缉a-5p调控的关键基因。
从五个miRNA相关数据库中获得了总共429个经实验验证的靶基因。miR-199a-5p及其经实验验证的靶基因在骨骼、大脑和皮肤中的表达升高。KEGG通路分析显示,靶基因在粘着斑、癌症中的微小RNA和河马信号通路中富集。生物学过程分类显示,大部分靶基因被归类为转录、DNA模板化。使用MalaCards和TargetScanhuman7.1鉴定出总共八个交集基因。筛选并验证了参与CL/P的miR-199a-5p的靶基因转化生长因子α(TGFA)。
MiR-199a-5p可能通过调控关键靶基因TGFA介导CL/P。该研究可能有助于更好地理解CL/P的病因。