基于生物信息学分析microRNA-495-5p在早产儿支气管肺发育不良中的表达及其临床意义

目的 探讨支气管肺发育不良（BPD）早产儿血清中microRNA-495-5p（miRNA-495-5p）的表达变化并对其进行生物信息学分析,为深入研究miRNA-495-5p与BPD的关系提供理论依据。方法 收集2015年1月至2016年12月NICU住院治疗早产儿的一般临床资料,选取具有早期BPD临床表现的20例患儿为BPD组,无早期BPD临床表现的20例患儿为对照组。采集两组患儿末梢外周血,每组各随机选取5例患儿,应用miRNA芯片技术筛选两组患儿血清中差异性表达的miRNAs;每组各随机选取6例患儿,采用RT-PCR技术再次验证其差异性表达。应用TargetScan、miRDB、miRWalk数据库对miRNA-495-5p进行靶基因预测;采用DAVID数据库对靶基因进行基因功能富集分析和信号转导通路富集分析。结果 与对照组患儿相比,BPD组患儿血清miRNA-495-5p表达显著上调（P < 0.05）。通过3种数据库预测miRNA-495-5p的靶基因共有117个,其靶基因功能分别富集于转录调节活性、转录激活活性、转录辅助激活活性等分子功能,代谢过程的调控、依赖DNA的转录调控、血管模式等生物学过程,以及核质、膜组分、不溶性组分等细胞组分上（P < 0.05）;信号转导通路则显著富集于mTOR信号通路中（P < 0.05）。结论 miRNA-495-5p可能通过调控新生血管生成、干细胞分化、细胞凋亡及自噬等参与BPD的发生发展,为后续深入研究其在BPD中的作用及功能机制提供了重要线索。

Expression of microRNA-495-5p in preterm infants with bronchopulmonary dysplasia: a bioinformatics analysis

Objective To study the expression of microRNA-495-5p (miRNA-495-5p) in the serum of preterm infants with bronchopulmonary dysplasia (BPD) based on a bioinformatics analysis, and to provide a theoretical basis for further research on the association between miRNA-495-5p and BPD. Methods A total of 40 preterm infants who were admitted to the neonatal intensive care unit from January 2015 to December 2016 were enrolled. Among these infants, 20 with early clinical manifestations of BPD were enrolled as the BPD group, and 20 without such manifestations were enrolled as the control group. Peripheral blood samples were collected. The miRNA microarray technique was used to screen out differentially expressed miRNAs in serum between the two groups. RT-PCR was used for validation of results. TargetScan, miRDB, and miRWalk databases were used to predict the target genes of miRNA-495-5p. The DAVID database was used to perform gene ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis of the target genes. Results Compared with the control group, the BPD group had a significant increase in the expression of miRNA-495-5p in serum (P < 0.05). A total of 117 target genes of miRNA-495-5p were predicted by the above three databases and they were involved in several molecular functions (including transcriptional regulatory activity, transcriptional activation activity, and transcription cofactor activity), biological processes (such as metabolic regulation, DNA-dependent transcriptional regulation, and vascular pattern), and cell components (including nucleoplasm, membrane components, and insoluble components) (P < 0.05). As for signaling pathways, these genes were significantly enriched in the mTOR signaling pathway (P < 0.05). Conclusions MiRNA-495-5p may be involved in the development and progression of BPD by regulating angiogenesis, stem cell differentiation, apoptosis, and autophagy, which provides clues for further research on the role and functional mechanism of miRNA-495-5p in BPD.