microRNA-296-5p靶基因的预测及在肺发育中的应用

张颖慧; 杨洋; 张存; 孙祎璠; 朱雯; 马程玲; 周晓玉

doi:10.7499/j.issn.1008-8830.2016.12.021

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中国当代儿科杂志 ›› 2016, Vol. 18 ›› Issue (12) : 1302-1307. DOI: 10.7499/j.issn.1008-8830.2016.12.021

论著·实验研究

microRNA-296-5p靶基因的预测及在肺发育中的应用

张颖慧, 杨洋, 张存, 孙祎璠, 朱雯, 马程玲, 周晓玉

作者信息 +

Prediction of microRNA-296-5p target genes and its application in lung development

ZHANG Ying-Hui, YANG Yang, ZHANG Cun, SUN Yi-Fan, ZHU Wen, MA Cheng-Ling, ZHOU Xiao-Yu

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文章历史 +

摘要

目的对rno-microRNA-296-5p（miR-296）靶基因预测并进行相关生物信息学分析，为深入研究miR-296与胎肺发育相关的生物学功能提供理论依据。方法应用PubMed、Google等信息搜索工具检索miR-296的现有研究，并通过miRBase获取其序列特征以及进化的保守性；利用TargetScan数据库进行miR-296的靶基因预测；并利用DAVID Bioinformatics Resources 6.8数据库对靶基因进行功能富集分析；利用KEGG数据库对靶基因进行信号转导通路分析。结果已有的文献表明miR-296在许多生物学过程中发挥重要作用，序列在多物种间高度保守。miR-296调控的靶基因参与分子功能、细胞组分和生物学过程等方面，靶基因集合的信号转导通路显著富集于MAPK信号通路、Wnt信号通路、TGF-β信号通路等（均P < 0.05）。结论通过对miR-296靶基因的生物信息学分析，为研究miR-296在肺发育中的作用提供了功能与机制的线索。

Abstract

Objective To predict the target genes of rno-microRNA-296-5p (miR-296) using bioinformatics software and databases, and to provide a theoretical basis for further studies of biological effects of miR-296 in fetal lung development. Methods PubMed and Google were used to search for all reported literature on miR-296. The miRBase database was used to determine the sequence and evolutionary conservatism of miR-296. The TargetScans database was used to predict the target genes of miR-296. The DAVID Bioinformatics Resources 6.8 database was used for the functional enrichment analysis of the target genes. The KEGG database was used to analyze the signaling pathways of target genes. Results miR-296 was reported to play important roles in many biological processes and have a high degree of sequence conservation among species. The target genes of miR-296 were involved in biological processes, cell components, and molecular function. Those target genes were significantly enriched in the mitogen-activated protein kinase signaling pathway, Wnt signaling pathway, and transforming growth factor-β signaling pathway (P < 0.05). Conclusions The bioinformatics analysis of the target genes of miR-296 provides a basis for studying biological effects and mechanism of action of miR-296 in lung development.

导出引用

张颖慧, 杨洋, 张存, 孙祎璠, 朱雯, 马程玲, 周晓玉. microRNA-296-5p靶基因的预测及在肺发育中的应用[J]. 中国当代儿科杂志. 2016, 18(12): 1302-1307 https://doi.org/10.7499/j.issn.1008-8830.2016.12.021

ZHANG Ying-Hui, YANG Yang, ZHANG Cun, SUN Yi-Fan, ZHU Wen, MA Cheng-Ling, ZHOU Xiao-Yu. Prediction of microRNA-296-5p target genes and its application in lung development[J]. Chinese Journal of Contemporary Pediatrics. 2016, 18(12): 1302-1307 https://doi.org/10.7499/j.issn.1008-8830.2016.12.021

参考文献

[1] Cardoso WV, Lü J. Regulation of early lung morphogenesis:questions, facts and controversies[J]. Development, 2006, 133(9):1611-1624.
[2] Wu L, Fan J, Belasco JG. MicroRNAs direct rapid deadenylation of mRNA[J]. Proc Natl Acad Sci U S A, 2006, 103(11):4034-4039.
[3] Yang Y, Kai G, Pu XD, et al. Expression profile of microRNAs in fetal lung development of Sprague-Dawley rats[J]. Int J Mol Med, 2012, 29(3):393-402.
[4] Xu C, Li S, Chen T, et al. miR-296-5p suppresses cell viability by directly targeting PLK1 in non-small cell lung cancer[J]. Oncol Rep, 2016, 35(1):497-503.
[5] Yan W, Chen J, Chen Z, et al. Deregulated miR-296/S100A4 axis promotes tumor invasion by inducing epithelial-mesenchymal transition in human ovarian cancer[J]. Am J Cancer Res, 2016, 6(2):260-269.
[6] Lee H, Hwang SJ, Kim HR, et al. Neurofibromatosis 2(NF2) controls the invasiveness of glioblastoma through YAP-dependent expression of CYR61/CCN1 and miR-296-3p[J]. Biochim Biophys Acta, 2016, 1859(4):599-611.
[7] Zheng Z, Ke X, Wang M, et al. Human microRNA hsa-miR-296-5p suppresses enterovirus 71 replication by targeting the viral genome[J]. J Virol, 2013, 87(10):5645-5656.
[8] Cazanave SC, Mott JL, Elmi NA, et al. A role for miR-296 in the regulation of lipoapoptosis by targeting PUMA[J]. J Lipid Res, 2011, 52(8):1517-1525.
[9] Feng J, Huang T, Huang Q, et al. Pro-angiogenic microRNA-296 upregulates vascular endothelial growth factor and downregulates Notch1 following cerebral ischemic injury[J]. Mol Med Rep, 2015, 12(6):8141-8147.
[10] Lewis BP, Burge CB, Bartel DP. Conserved seed pairing, often flanked by adenosines, indicates that thousands of human genes are microRNA targets[J]. Cell, 2005, 120(1):15-20.
[11] Bartel DP. MicroRNAs:genomics, biogenesis, mechanism, and function[J]. Cell, 2004, 116(2):281-297.
[12] Mujahid S, Logvinenko T, Volpe MV, et al. miRNA regulated pathways in late stage murine lung development[J]. BMC Dev Biol, 2013, 13:13.
[13] Lu Y, Thomson JM, Wong HY, et al. Transgenic over-expression of the microRNA miR-17-92 cluster promotes proliferation and inhibits differentiation of lung epithelial progenitor cells[J]. Dev Biol, 2007, 310(2):442-453.
[14] Bhaskaran M, Wang Y, Zhang H, et al. MicroRNA-127 modulates fetal lung development[J]. Physiol Genomics, 2009, 37(3):268-278.
[15] Wang L, Su W, Du W, et al. Gene and MicroRNA profiling of human induced pluripotent stem cell-derived endothelial cells[J]. Stem Cell Rev, 2015, 11(2):219-227.
[16] Ehrlich M, Horbelt D, Marom B, et al. Homomeric and heteromeric complexes among TGF-β and BMP receptors and their roles in signaling[J]. Cell Signal, 2011, 23(9):1424-1432.
[17] Warburton D, Bellusci S, De Langhe S, et al. Molecular mechanisms of early lung specification and branching morphogenesis[J]. Pediatr Res, 2005, 57(5 Pt 2):26R-37R.
[18] Xu B, Chen C, Chen H, et al. Smad1 and its target gene Wif1 coordinate BMP and Wnt signaling activities to regulate fetal lung development[J]. Development, 2011, 138(5):925-935.
[19] Weng T, Liu L. The role of pleiotrophin and beta-catenin in fetal lung development[J]. Respir Res, 2010, 11:80.
[20] Halwani R, Al-Muhsen S, Al-Jahdali H, et al. Role of transforming growth factor-β in airway remodeling in asthma[J]. Am J Respir Cell Mol Biol, 2011, 44(2):127-133.